Role of the sarcoplasmic reticulum in muscle cells

WEBVTT
Kind: captions
Language: en

00:00:00.750 --> 00:00:04.480
We know from the last video that
if we have a high calcium

00:00:04.480 --> 00:00:09.040
ion concentration inside of the
muscle cell, those calcium

00:00:09.040 --> 00:00:13.500
ions will bond to the troponin
proteins which will then

00:00:13.500 --> 00:00:17.140
change their shape in such a way
that the tropomyosin will

00:00:17.140 --> 00:00:20.580
be moved out of the way and so
then the myosin heads can

00:00:20.580 --> 00:00:23.310
crawl along the actin filaments
and them we'll

00:00:23.310 --> 00:00:24.950
actually have muscle
contractions.

00:00:24.950 --> 00:00:29.140
So high calcium concentration,
or calcium ion concentration,

00:00:29.140 --> 00:00:30.850
we have contraction.

00:00:30.850 --> 00:00:35.560
Low calcium ion concentration,
these troponin proteins go to

00:00:35.560 --> 00:00:39.060
their standard confirmation and
they pull-- or you can say

00:00:39.060 --> 00:00:42.600
they move the tropomyosin back
in the way of the myosin

00:00:42.600 --> 00:00:44.165
heads-- and we have
no contraction.

00:00:53.750 --> 00:00:57.140
So the next obvious question
is, how does the muscle

00:00:57.140 --> 00:00:59.850
regulate whether we have high
calcium concentration and

00:00:59.850 --> 00:01:03.350
contraction or low calcium
concentration and relaxation?

00:01:03.350 --> 00:01:04.940
Or even a better question
is, how does the

00:01:04.940 --> 00:01:05.830
nervous system do it?

00:01:05.830 --> 00:01:09.490
How does the nervous system tell
the muscle to contract,

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to make its calcium
concentration high and

00:01:11.550 --> 00:01:14.010
contract or to make it
low again and relax?

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And to understand that, let's
do a little bit a review of

00:01:17.900 --> 00:01:20.790
what we learned on the
videos on neurons.

00:01:20.790 --> 00:01:24.000
Let me draw the terminal
junction of

00:01:24.000 --> 00:01:27.500
an axon right here.

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Instead of having a synapse
with a dendrite of another

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neuron, it's going to have
a synapse with an

00:01:32.890 --> 00:01:35.130
actual muscle cell.

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So this is its synapse with
the actual muscle cell.

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This is a synapse with an
actual muscle cell.

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Let me label everything just
so you don't get confused.

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This is the axon.

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We could call it the terminal
end of an axon.

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This is the synapse.

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Just a little terminology from
the neuron videos-- this space

00:02:08.150 --> 00:02:10.210
was a synaptic cleft.

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This is the presynaptic
neuron.

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This is-- I guess you could
kind of view it-- the

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post-synaptic cell.

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It's not a neuron
in this case.

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And then just so we
have-- this is our

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membrane of muscle cell.

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And I'm going to do-- probably
the next video or maybe a

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video after that, I'll actually
show you the anatomy

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of a muscle cell.

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In this, it'll be a little
abstract because we really

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want to understand how
the calcium ion

00:02:39.300 --> 00:02:42.810
concentration is regulated.

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This is called a sarcolemma.

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So this is the membrane
of the muscle cell.

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And this right here-- you could
imagine it's just a fold

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into the membrane of
the muscle cell.

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If I were to look at the surface
of the muscle cell,

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then it would look like a little
bit of a hole or an

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indentation that goes into the
cell, but here we did a cross

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section so you can imagine it
folding in, but if you poked

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it in with a needle or
something, this is

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what you would get.

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You would get a fold
in the membrane.

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And this right here is
called a T-tubule.

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And the T just stands
for transverse.

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It's going transverse to the
surface of the membrane.

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And over here-- and this is the
really important thing in

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this video, or the
really important

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organelle in this video.

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You have this organelle inside
of the muscle cell called the

00:03:42.410 --> 00:03:43.890
sarcoplasmic reticulum.

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And it actually is very similar
to an endoplasmic

00:03:57.700 --> 00:04:03.180
reticulum in somewhat of what
it is or maybe how it's

00:04:03.180 --> 00:04:06.750
related to an endoplasmic
reiticulum-- but here its main

00:04:06.750 --> 00:04:07.760
function is storage.

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While an endoplasmic reticulum,
it's involved in

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protein development and it has
ribosomes attached to it, but

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this is purely a storage
organelle.

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What the sarcoplasmic reticulum
does it has calcium

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ion pumps on its membrane and
what these do is they're ATP

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ases, which means that they
use ATP to fuel the pump.

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So you have ATP come in, ATP
attaches to it, and maybe a

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calcium ion will attach to it,
and when the ATP hydrolyzes

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into ADP plus a phosphate
group, that changes the

00:05:01.470 --> 00:05:04.140
confirmation of this protein
and it pumps

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the calcium ion in.

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So the calcium ions
get pumped in.

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So the net effect of all of
these calcium ion pumps on the

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membrane of the sarcoplasmic
reticulum is in a resting

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muscle, we'll have a very high
concentration of calcium ions

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on the inside.

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Now, I think you could
probably guess

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where this is going.

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When the muscle needs to
contract, these calcium ions

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get dumped out into the
cytoplasm of the cell.

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And then they're able to bond
to the troponin right here,

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and do everything we talked
about in the last video.

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So what we care about is, just
how does it know when to dump

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its calcium ions into the
rest of the cell?

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This is the inside
of the cell.

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And so this area is what the
actin filaments and the myosin

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heads and all of the rest,
and the troponin, and the

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tropomyosin-- they're all
exposed to the environment

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that is over here.

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So you can imagine-- I could
just draw it here

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just to make it clear.

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I'm drawing it very abstract.

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We'll see more of the structure
in a future video.

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This is a very abstract drawing,
but I think this'll

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give you a sense of
what's going on.

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So let's say this neuron-- and
we'll call this a motor

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neuron-- it's signaling for
a muscle contraction.

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So first of all, we know how
signals travel across neurons,

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especially across axons with
an action potential.

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We could have a sodium
channel right here.

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It's voltage gated so you have
a little bit of a positive

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voltage there.

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That tells this voltage gated
sodium channel to open up.

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So it opens up and allows even
more of the sodium to flow in.

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That makes it a little bit
more positive here.

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So then that triggers the next
voltage gated channel to open

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up-- and so it keeps traveling
down the membrane of the

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axon-- and eventually, when you
get enough of a positive

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threshold, voltage gated calcium
channels open up.

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This is all a review
of what we learned

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in the neuron videos.

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So eventually, when it gets
positive enough close to these

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calcium ion channels, they
allow the calcium

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ions to flow in.

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And the calcium ions flow in and
they bond to those special

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proteins near the synaptic
membrane or the presynaptic

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membrane right there.

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These are calcium ions.

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They bond to proteins that
were docking vesicles.

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Remember, vesicles were just
these membranes around

00:08:08.170 --> 00:08:09.420
neurotransmitters.

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When the calcium binds to those
proteins, it allows

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exocytosis to occur.

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It allows the membrane of the
vesicles to merge with the

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membrane of the actual
neuron and the

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contents get dumped out.

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This is all review from
the neuron videos.

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I explained it in much more
detail in those videos, but

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you have-- all of these

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neurotransmitters get dumped out.

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And we were talking about the
synapse between a neuron and a

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muscle cell.

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The neurotransmitter
here is acetylcholine.

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But just like what would happen
at a dendrite, the

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acetylcholine binds to receptors
on the sarcolemma or

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the membrane of the muscle cell
and that opens sodium

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channels on the muscle cell.

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So the muscle cell also has a a
voltage gradient across its

00:09:02.330 --> 00:09:07.210
membrane, just like
a neuron does.

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So when this guy gets some
acetylcholene, it allows

00:09:11.150 --> 00:09:16.240
sodium to flow inside
the muscle cell.

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So you have a plus there and
that causes an action

00:09:18.580 --> 00:09:19.990
potential in the muscle cell.

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So then you have a little bit
of a positive charge.

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If it gets high enough to a
threshold level, it'll trigger

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this voltage gated channel right
here, which will allow

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more sodium to flow in.

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So it'll become a little
bit positive over here.

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Of course, it also has potassium
to reverse it.

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It's just like what's going
on in a neuron.

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So eventually this action
potential-- you have a sodium

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channel over here.

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It gets a little bit positive.

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When it gets enough positive,
then it opens up and allows

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even more sodium to flow in.

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So you have this action
potential.

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and then that action potential--
so you have a

00:09:53.230 --> 00:09:57.950
sodium channel over here-- it
goes down this T-tubule.

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So the information from the
neuron-- you could imagine the

00:10:00.230 --> 00:10:03.930
action potential then turns into
kind of a chemical signal

00:10:03.930 --> 00:10:06.370
which triggers another
action potential that

00:10:06.370 --> 00:10:07.880
goes down the T-tubule.

00:10:07.880 --> 00:10:10.560
And this is the interesting
part-- and actually this is an

00:10:10.560 --> 00:10:13.670
area of open research right
now and I'll give you some

00:10:13.670 --> 00:10:17.860
leads if you want to read more
about this research-- is that

00:10:17.860 --> 00:10:20.940
you have a protein complex that
essentially bridges the

00:10:20.940 --> 00:10:23.010
sarcoplasmic reticulum
to the T-tubule.

00:10:23.010 --> 00:10:28.600
And I'll just draw it as
a big box right here.

00:10:28.600 --> 00:10:31.180
So you have this protein
complex right there.

00:10:31.180 --> 00:10:34.970
And I'll actually show it--
people believe-- I'll sort

00:10:34.970 --> 00:10:36.270
some words out here.

00:10:36.270 --> 00:10:44.170
It involves the proteins
triadin, junctin,

00:10:44.170 --> 00:10:51.180
calsequestrin, and ryanodine.

00:10:56.290 --> 00:10:59.550
But they're somehow involved in
a protein complex here that

00:10:59.550 --> 00:11:04.550
bridges between the T-tubule the
sarcoplasmic reticulum,

00:11:04.550 --> 00:11:06.720
but the big picture is what
happens when this action

00:11:06.720 --> 00:11:09.880
potential travels down here--
so we get positive enough

00:11:09.880 --> 00:11:16.280
right around here, this complex
of proteins triggers

00:11:16.280 --> 00:11:17.610
the release of calcium.

00:11:17.610 --> 00:11:20.920
And they think that the
ryanodine is actually the part

00:11:20.920 --> 00:11:23.930
that actually releases the
calcium, but we could just say

00:11:23.930 --> 00:11:27.790
that it-- maybe it's triggered
right here.

00:11:27.790 --> 00:11:30.330
When the action potential
travels down-- let me switch

00:11:30.330 --> 00:11:31.010
to another color.

00:11:31.010 --> 00:11:33.100
I'm using this purple
too much.

00:11:33.100 --> 00:11:36.980
When the action potential gets
far enough-- I'll use red

00:11:36.980 --> 00:11:40.070
right here-- when the action
potential gets far enough-- so

00:11:40.070 --> 00:11:42.260
this environment gets a little
positive with all those sodium

00:11:42.260 --> 00:11:45.920
ions flowing in, this mystery
box-- and you could do web

00:11:45.920 --> 00:11:47.100
searches for these proteins.

00:11:47.100 --> 00:11:49.030
People are still trying to
understand exactly how this

00:11:49.030 --> 00:11:52.570
mystery box works-- it triggers
an opening for all of

00:11:52.570 --> 00:11:57.290
these calcium ions to escape
the sarcoplasmic reticulum.

00:11:57.290 --> 00:12:03.870
So then all these calcium ions
get dumped into the outside of

00:12:03.870 --> 00:12:07.610
the sarcoplasmic reticulum
into-- just the inside of the

00:12:07.610 --> 00:12:10.230
cell, into the cytoplasm
of the cell.

00:12:10.230 --> 00:12:12.550
Now when that happens, what's
doing to happen?

00:12:12.550 --> 00:12:14.670
Well, the high calcium
concentration, the calcium

00:12:14.670 --> 00:12:17.390
ions bond to the troponin, just
like what we said at the

00:12:17.390 --> 00:12:18.750
beginning of the video.

00:12:18.750 --> 00:12:23.390
The calcium ions bond to the
troponin, move the tropomyosin

00:12:23.390 --> 00:12:26.520
out of the way, and then the
myosin using ATP like we

00:12:26.520 --> 00:12:30.050
learned two videos ago can start
crawling up the actin--

00:12:30.050 --> 00:12:35.030
and at the same time, once the
signal disappears, this thing

00:12:35.030 --> 00:12:39.290
shuts down and then these
calcium ion pumps will reduce

00:12:39.290 --> 00:12:41.180
the calcium ion concentration
again.

00:12:41.180 --> 00:12:45.070
And then our contraction will
stop and the muscle will get

00:12:45.070 --> 00:12:46.090
relaxed again.

00:12:46.090 --> 00:12:49.070
So the whole big thing here is
that we have this container of

00:12:49.070 --> 00:12:52.440
calcium ions that, when the
muscles relax, is essentially

00:12:52.440 --> 00:12:55.330
taking the calcium ions out of
the inside of the cell so the

00:12:55.330 --> 00:12:58.830
muscle is relaxed so that you
can't have your myosin climb

00:12:58.830 --> 00:13:00.330
up the actin.

00:13:00.330 --> 00:13:03.190
But then when it gets the
signal, it dumps it back in

00:13:03.190 --> 00:13:06.040
and then we actually have a
muscle contraction because the

00:13:06.040 --> 00:13:11.280
tropomyosin gets moved out of
the way by the troponin., So I

00:13:11.280 --> 00:13:12.090
don't know.
That's pretty fascinating.

00:13:12.090 --> 00:13:14.160
It's actually even fascinating
that this is still not

00:13:14.160 --> 00:13:16.200
completely well understood.

00:13:16.200 --> 00:13:19.140
This is an active-- if you want
to become a biological

00:13:19.140 --> 00:13:21.360
researcher, this could be an
interesting thing to try to

00:13:21.360 --> 00:13:22.330
understand.

00:13:22.330 --> 00:13:25.740
One, it's interesting just from
a scientific point of

00:13:25.740 --> 00:13:27.900
view of how this actually
functions, but there's

00:13:27.900 --> 00:13:31.630
actually-- there's maybe
potential diseases that are

00:13:31.630 --> 00:13:34.210
byproducts of malfunctioning
proteins right here.

00:13:34.210 --> 00:13:37.050
Maybe you can somehow make these
things perform better or

00:13:37.050 --> 00:13:37.770
worse, or who knows.

00:13:37.770 --> 00:13:41.960
So there actually are positive
impacts that you could have if

00:13:41.960 --> 00:13:44.750
you actually figured out what
exactly is going on here when

00:13:44.750 --> 00:13:47.440
the action potential
shows up to open up

00:13:47.440 --> 00:13:48.490
this calcium channel.

00:13:48.490 --> 00:13:49.770
So now we have the
big picture.

00:13:49.770 --> 00:13:53.770
We know how a motor neuron can
stimulate a contraction of a

00:13:53.770 --> 00:14:00.240
cell by allowing the
sarcoplasmic reticulum to

00:14:00.240 --> 00:14:03.490
allow calcium ions to travel
across this membrane in the

00:14:03.490 --> 00:14:04.590
cytoplasm of the cell.

00:14:04.590 --> 00:14:07.240
And I was doing a little bit of
reading before this video.

00:14:07.240 --> 00:14:08.740
These pumps are very
efficient.

00:14:08.740 --> 00:14:11.980
So once the signal goes away and
this door is closed right

00:14:11.980 --> 00:14:16.900
here, this this sarcoplasmic
reticulum can get back the ion

00:14:16.900 --> 00:14:19.070
concentration in about
30 milliseconds.

00:14:19.070 --> 00:14:22.100
So that's why we're so good at
stopping contractions, why I

00:14:22.100 --> 00:14:25.820
can punch and then pull back my
arm and then have it relax

00:14:25.820 --> 00:14:28.870
all within split-seconds
because we can stop the

00:14:28.870 --> 00:14:33.520
contraction in 30 milliseconds,
which is less

00:14:33.520 --> 00:14:34.670
than 1/30 of a second.

00:14:34.670 --> 00:14:37.500
So anyway, I'll see in the next
video, where we'll study

00:14:37.500 --> 00:14:40.030
the actual anatomy of
a muscle cell in a

00:14:40.030 --> 00:14:41.840
little bit more detail.


How tropomyosin and troponin regulate muscle contraction

WEBVTT
Kind: captions
Language: en

00:00:00.400 --> 00:00:04.230
In the last video, we learned
how myosin-- and myosin II in

00:00:04.230 --> 00:00:06.370
particular-- when we say myosin
II it actually has two

00:00:06.370 --> 00:00:09.460
of these myosin heads and their
tails are inter-wound

00:00:09.460 --> 00:00:13.040
with each other-- how myosin
II can use ATP to

00:00:13.040 --> 00:00:16.550
essentially-- you can almost
imagine either pulling an

00:00:16.550 --> 00:00:19.385
actin filament or walking
up an actin filament.

00:00:19.385 --> 00:00:20.930
It starts attached.

00:00:20.930 --> 00:00:23.080
ATP comes and bonds onto it.

00:00:23.080 --> 00:00:25.370
That causes it to be released.

00:00:25.370 --> 00:00:31.650
Then the ATP hydrolyzes into
ADP and a phosphate group.

00:00:31.650 --> 00:00:33.795
And when that happens, that
energy's released.

00:00:33.795 --> 00:00:35.620
It puts this into a higher
energy state.

00:00:35.620 --> 00:00:39.910
It kind of spring-loads the
protein and then it attaches

00:00:39.910 --> 00:00:44.070
up another notch on the actual
actin filament and then the

00:00:44.070 --> 00:00:47.290
phosphate group leaves and
that's where the confirmation

00:00:47.290 --> 00:00:49.760
change in this protein
is enough.

00:00:49.760 --> 00:00:52.660
It generates the power stroke to
actually push on the actin

00:00:52.660 --> 00:00:55.480
filament-- and you could
imagine, either move the

00:00:55.480 --> 00:01:00.240
myosin-- whatever the myosin is
connected to-- to the left

00:01:00.240 --> 00:01:02.610
or whatever the actin is
connected to to the right.

00:01:02.610 --> 00:01:05.010
We're going to talk a lot more
about what they're connected

00:01:05.010 --> 00:01:06.460
to in future videos.

00:01:06.460 --> 00:01:09.130
Now, a couple of questions
might have been

00:01:09.130 --> 00:01:10.800
raising in your head.

00:01:10.800 --> 00:01:13.630
This guy had so much effort to
pull on this thing, right?

00:01:13.630 --> 00:01:16.870
There's some tension pulling in
the other direction, right?

00:01:16.870 --> 00:01:19.870
I said this is what happens in
muscles, so there must be some

00:01:19.870 --> 00:01:21.760
weight or some other
resistance.

00:01:21.760 --> 00:01:25.200
So what happens when
this releases?

00:01:25.200 --> 00:01:28.990
At the first step when ATP
joined and this released,

00:01:28.990 --> 00:01:32.440
wouldn't the actin filament
just go back to

00:01:32.440 --> 00:01:33.370
where it was before?

00:01:33.370 --> 00:01:35.180
Especially if there's
some tension on it

00:01:35.180 --> 00:01:37.520
going in that direction.

00:01:37.520 --> 00:01:42.150
And the simple answer to that
is, this isn't the only myosin

00:01:42.150 --> 00:01:45.140
protein that's acting
on this actin.

00:01:45.140 --> 00:01:47.380
You have others all
along the chain.

00:01:47.380 --> 00:01:48.740
Maybe you have one
right there.

00:01:48.740 --> 00:01:50.640
Maybe you have one
right there.

00:01:50.640 --> 00:01:53.150
They're all working at their own
pace at different times.

00:01:53.150 --> 00:01:55.550
So you have so many of these
that when one of them is

00:01:55.550 --> 00:01:57.840
disengaged, another one of them
might be in their power

00:01:57.840 --> 00:01:59.980
stroke or another one
might be engaged.

00:01:59.980 --> 00:02:02.750
So it's not like you have this
notion of, if all of a sudden

00:02:02.750 --> 00:02:06.240
one lets go, that the actin
filament will recoil back to

00:02:06.240 --> 00:02:07.210
where it was.

00:02:07.210 --> 00:02:11.600
Now the next question that you
might be thinking is, how do I

00:02:11.600 --> 00:02:13.990
turn on and off this
situation?

00:02:13.990 --> 00:02:16.590
We have command over
our muscles.

00:02:16.590 --> 00:02:20.490
What can turn on or off this
system of the myosin

00:02:20.490 --> 00:02:22.690
essentially crawling
up the actin?

00:02:22.690 --> 00:02:25.460
And to understand that, there's
two other proteins

00:02:25.460 --> 00:02:26.900
that come into effect.

00:02:26.900 --> 00:02:28.880
That's tropomyosin
and troponin.

00:02:48.270 --> 00:02:51.760
And so I'm going to redraw the
actin-- I'll do a very rough

00:02:51.760 --> 00:02:53.910
drawing of the actin filament.

00:02:53.910 --> 00:02:56.190
Let's say that that's my actin
filament right there with its

00:02:56.190 --> 00:02:56.790
little grooves.

00:02:56.790 --> 00:02:58.040
It's actually a helical
structure.

00:03:05.630 --> 00:03:08.080
And actually, these grooves--
it's kind of a helical-- but

00:03:08.080 --> 00:03:10.010
we won't worry too
much about that.

00:03:10.010 --> 00:03:15.550
What we drew so far, at least
in the last video, you had

00:03:15.550 --> 00:03:16.490
these little myosin.

00:03:16.490 --> 00:03:18.860
You can view them as feet or
head or whatever that keep

00:03:18.860 --> 00:03:21.490
attaching to it and then based
on where they are in that ATP

00:03:21.490 --> 00:03:23.700
cycle, they can keep getting
cranked back up or

00:03:23.700 --> 00:03:26.650
spring-loaded and go to the
next one and push back.

00:03:26.650 --> 00:03:29.650
Now, on top of this actin,
you actually have

00:03:29.650 --> 00:03:31.160
this tropomyosin protein.

00:03:31.160 --> 00:03:38.030
And this tropomyosin protein,
it coils around the actin.

00:03:38.030 --> 00:03:41.270
So this is our actin
right here.

00:03:41.270 --> 00:03:44.760
This is one of the two heads
of the myosin II.

00:03:47.830 --> 00:03:49.990
And then we have our
tropomyosin.

00:03:49.990 --> 00:03:51.972
Tropomyosin is coiled around.

00:03:51.972 --> 00:03:55.260
It's a very rough sketch, but
you can imagine it's coiled

00:03:55.260 --> 00:04:00.000
around and it goes back behind
it, then it goes like that,

00:04:00.000 --> 00:04:03.400
and then it goes back behind
it, then it goes like that.

00:04:03.400 --> 00:04:06.040
So it's coiled around it and the
important thing about it

00:04:06.040 --> 00:04:10.210
is, if there's-- let me
take a step back.

00:04:10.210 --> 00:04:13.860
It's coiled around and it's
attached to the actin by

00:04:13.860 --> 00:04:15.260
another protein called
troponin.

00:04:17.959 --> 00:04:20.860
Let's say it's attached there
and-- this isn't exact, but

00:04:20.860 --> 00:04:25.270
let's say it's attached there,
and there, and there, and

00:04:25.270 --> 00:04:27.610
there, and there by
the troponin.

00:04:27.610 --> 00:04:28.860
So let me write this down.

00:04:40.200 --> 00:04:43.540
So you can imagine, the troponin
is kind of like the

00:04:43.540 --> 00:04:44.790
nails into the actin.

00:04:44.790 --> 00:04:48.050
So it dictates where
the tropomyosin is.

00:04:48.050 --> 00:04:54.040
So when a muscle is not
contracting, it turns out that

00:04:54.040 --> 00:04:57.970
the tropomyosin is blocking
the myosin from being able

00:04:57.970 --> 00:05:00.690
to-- and I've read a bunch of
accounts on this and I think

00:05:00.690 --> 00:05:02.490
this is still an area
of research.

00:05:02.490 --> 00:05:04.690
It's not 100% clear one
way or the other.

00:05:04.690 --> 00:05:08.850
Tropomyosin is-- or maybe both--
blocking the myosin

00:05:08.850 --> 00:05:11.880
from being able to attach to
the actin where it normally

00:05:11.880 --> 00:05:15.630
attaches so it won't be able
to crawl up the actin-- or

00:05:15.630 --> 00:05:18.090
sometimes the myosin is attached
to the actin, but it

00:05:18.090 --> 00:05:21.840
keeps it from releasing and
sliding up the actin to keep

00:05:21.840 --> 00:05:23.280
that walking procedure.

00:05:23.280 --> 00:05:27.500
So the bottom line is that
this tropomyosin kind of

00:05:27.500 --> 00:05:42.940
blocks the myosin head-- this
is the myosin head right

00:05:42.940 --> 00:05:55.770
there-- from crawling up the
actin, either by physically

00:05:55.770 --> 00:05:59.740
blocking its actual binding site
or if it's already bound,

00:05:59.740 --> 00:06:02.480
keeping it from being able to
keep sliding up the actin.

00:06:02.480 --> 00:06:05.310
Either way, it's blocking it
and the only way to make it

00:06:05.310 --> 00:06:08.240
unblocked is for the troponins
to actually change their

00:06:08.240 --> 00:06:10.570
confirmation, for them to
change their shape.

00:06:10.570 --> 00:06:13.330
And the only way for them to
change their shape is if we

00:06:13.330 --> 00:06:17.380
have a high calcium
ion concentration.

00:06:17.380 --> 00:06:23.300
So if you have a bunch of
calcium ions, if you have a

00:06:23.300 --> 00:06:26.350
high enough concentration, these
calcium ions are going

00:06:26.350 --> 00:06:31.750
to bond to the troponin and
then that changes the

00:06:31.750 --> 00:06:35.970
confirmation of the troponin
enough to move the

00:06:35.970 --> 00:06:38.350
configuration of the
tropomyosin.

00:06:38.350 --> 00:06:40.260
So let me write this down.

00:06:40.260 --> 00:06:43.130
So normally, tropomyosin blocks,
but then when you have

00:06:43.130 --> 00:06:52.070
a high calcium ion
concentration, they bind to

00:06:52.070 --> 00:06:59.840
troponin and then the troponin,
they change their

00:06:59.840 --> 00:07:02.850
confirmation so it moves the
tropomyosin out of the way.

00:07:14.510 --> 00:07:17.690
So when it moves out of the way,
you have a high calcium

00:07:17.690 --> 00:07:21.360
concentration, bonds troponin,
moves tropomyosin out of the

00:07:21.360 --> 00:07:23.770
way, then all of a sudden what
we talked about in the last

00:07:23.770 --> 00:07:26.860
video-- these guys can start
walking up the actin or

00:07:26.860 --> 00:07:29.180
pushing the actin to the
right, however you

00:07:29.180 --> 00:07:30.210
want to view it.

00:07:30.210 --> 00:07:38.300
But then if the calcium
concentration goes low, then

00:07:38.300 --> 00:07:40.620
the calciums get released
from the troponin.

00:07:40.620 --> 00:07:42.380
You need to have enough to
always hang around here.

00:07:42.380 --> 00:07:44.620
If the concentration becomes
really low here, these guys

00:07:44.620 --> 00:07:52.210
will start to leave. So then the
troponin goes back to, I

00:07:52.210 --> 00:07:53.460
guess, standard confirmation.

00:07:57.920 --> 00:08:05.530
That makes the tropomyosin
block the myosin again.

00:08:12.730 --> 00:08:14.770
So it's actually-- I
mean, I can't say

00:08:14.770 --> 00:08:15.780
anything here is simple.

00:08:15.780 --> 00:08:19.820
This was only discovered maybe
50 or 60 years ago and you can

00:08:19.820 --> 00:08:22.210
imagine to actually observe
these things or to create

00:08:22.210 --> 00:08:24.840
experiments to definitively
know what's happening--

00:08:24.840 --> 00:08:28.560
nothing is simple, but
the idea is simple.

00:08:28.560 --> 00:08:32.490
Without calcium, the tropomyosin
is blocking the

00:08:32.490 --> 00:08:34.549
ability of the myosin to attach
where it needs to

00:08:34.549 --> 00:08:38.559
attach or slide up the actin so
it can keep pushing on it.

00:08:38.559 --> 00:08:41.049
But if the calcium concentration
is high enough,

00:08:41.049 --> 00:08:43.610
they will bond to the troponin--
which essentially

00:08:43.610 --> 00:08:48.970
nails down the tropomyosin
that's wound around the actin

00:08:48.970 --> 00:08:51.630
and when they change their
confirmation with the calcium

00:08:51.630 --> 00:08:57.470
ions, it moves the tropomyosin
out of the way so that the

00:08:57.470 --> 00:08:59.590
myosin can do what it does.

00:08:59.590 --> 00:09:03.430
So you can imagine already,
we're building up a way for--

00:09:03.430 --> 00:09:05.830
one, for muscles to contract,
but even better, for us to

00:09:05.830 --> 00:09:07.570
control muscles to contract.

00:09:07.570 --> 00:09:11.540
So if we have a high calcium
concentration within the cell,

00:09:11.540 --> 00:09:13.050
the muscle will contract.

00:09:13.050 --> 00:09:16.060
If we have a low calcium
concentration again, then all

00:09:16.060 --> 00:09:17.700
of a sudden, these
will release.

00:09:17.700 --> 00:09:20.990
They'll be blocked, and then the
muscle will relax again.


Myosin and actin

WEBVTT
Kind: captions
Language: en

00:00:00.390 --> 00:00:03.370
What I want to do in this video
is try to understand how

00:00:03.370 --> 00:00:07.960
two proteins can interact with
each other in conjunction with

00:00:07.960 --> 00:00:12.210
ATP to actually produce
mechanical motion.

00:00:12.210 --> 00:00:15.320
And the reason why I want to
do this-- one, it occurs

00:00:15.320 --> 00:00:17.570
outside of muscle cells as well,
but this is really going

00:00:17.570 --> 00:00:20.025
to be the first video on really
how muscles work.

00:00:20.025 --> 00:00:23.310
And then we'll talk about how
nerves actually stimulate

00:00:23.310 --> 00:00:24.080
muscles to work.

00:00:24.080 --> 00:00:26.580
So it'll all build up
from this video.

00:00:26.580 --> 00:00:30.000
So what I've done here is I've
copy and pasted two images of

00:00:30.000 --> 00:00:31.480
proteins from Wikipedia.

00:00:31.480 --> 00:00:34.470
This is myosin.

00:00:34.470 --> 00:00:37.110
It's actually myosin II because
you actually have two

00:00:37.110 --> 00:00:39.410
strands of the myosin protein.

00:00:39.410 --> 00:00:42.150
They're interwound around each
other so you can see it's this

00:00:42.150 --> 00:00:46.040
very complex looking protein or
enzyme, however you want to

00:00:46.040 --> 00:00:46.696
talk about it.

00:00:46.696 --> 00:00:48.430
I'll tell you why it's called
an enzyme-- because it

00:00:48.430 --> 00:00:53.030
actually helps react ATP into
ADP and phosphate groups.

00:00:53.030 --> 00:00:55.460
So that's why it's
called an ATPase.

00:00:55.460 --> 00:00:59.150
It's a subclass of the
ATPase enzymes.

00:00:59.150 --> 00:01:02.530
This right here is actin.

00:01:02.530 --> 00:01:06.850
What we're going to see in
this video is how myosin

00:01:06.850 --> 00:01:10.920
essentially uses the ATP to
essentially crawl along.

00:01:10.920 --> 00:01:13.830
You can almost view it as an
actin rope and that's what

00:01:13.830 --> 00:01:15.790
creates mechanical energy.

00:01:15.790 --> 00:01:16.490
So let me draw it.

00:01:16.490 --> 00:01:19.240
I'll actually draw it on
this actin right here.

00:01:19.240 --> 00:01:23.280
So let's say we have one
of these myosin heads.

00:01:23.280 --> 00:01:25.740
So when I say a myosin head,
this is one of the myosin

00:01:25.740 --> 00:01:29.140
heads right here and then it's
connected, it's interwound,

00:01:29.140 --> 00:01:30.060
it's woven around.

00:01:30.060 --> 00:01:32.630
This is the other one and it
winds around that way.

00:01:32.630 --> 00:01:33.900
Now let's just say we're
just dealing with one

00:01:33.900 --> 00:01:35.730
of the myosin heads.

00:01:35.730 --> 00:01:37.050
Let's say it's in
this position.

00:01:37.050 --> 00:01:39.450
Let me see how well
I can draw it.

00:01:39.450 --> 00:01:44.370
Let's say it starts off in a
position that looks like that

00:01:44.370 --> 00:01:48.650
and then this is kind of the
tail part that connects to

00:01:48.650 --> 00:01:50.480
some other structural and we'll
talk about that in more

00:01:50.480 --> 00:01:53.580
detail, but this is my myosin
head right there in its

00:01:53.580 --> 00:01:56.490
starting position, not
doing anything.

00:01:56.490 --> 00:02:01.990
Now, ATP can come along and bond
to this myosin head, this

00:02:01.990 --> 00:02:05.940
enzyme, this protein,
this ATPase enzyme.

00:02:05.940 --> 00:02:09.210
So let me draw some ATP.

00:02:09.210 --> 00:02:12.820
So ATP comes along and bonds
to this guy right here.

00:02:12.820 --> 00:02:14.850
Let's say that's the-- and it's
not going to be this big

00:02:14.850 --> 00:02:16.940
relative to the protein,
but this is just to

00:02:16.940 --> 00:02:18.240
give you the idea.

00:02:18.240 --> 00:02:24.120
So soon as the ATP binds to its
appropriate site on this

00:02:24.120 --> 00:02:28.400
enzyme or protein, the enzyme,
it detaches from the actin.

00:02:28.400 --> 00:02:31.520
So let me write this down.

00:02:31.520 --> 00:02:44.560
So one, ATP binds to myosin
head and as soon as that

00:02:44.560 --> 00:02:58.390
happens, that causes the myosin
to release actin.

00:02:58.390 --> 00:02:59.720
So that's step one.

00:02:59.720 --> 00:03:03.050
So I start it off with this guy
just touching the actin,

00:03:03.050 --> 00:03:05.570
the ATP comes, and
it gets released.

00:03:05.570 --> 00:03:09.570
So in the next step-- so after
that step, it's going to look

00:03:09.570 --> 00:03:10.815
something like this--
and I want to draw

00:03:10.815 --> 00:03:11.990
it in the same place.

00:03:11.990 --> 00:03:13.300
After the next step,
it's going to look

00:03:13.300 --> 00:03:14.810
something like this.

00:03:14.810 --> 00:03:16.060
It will have released.

00:03:19.910 --> 00:03:25.160
So now it looks something like
that and you have the ATP

00:03:25.160 --> 00:03:26.870
attached to it still.

00:03:26.870 --> 00:03:28.970
I know it might be a little
bit convoluted when I keep

00:03:28.970 --> 00:03:30.450
writing over the same thing,
but you have the

00:03:30.450 --> 00:03:31.610
ATP attached to it.

00:03:31.610 --> 00:03:35.320
Now the next step-- the ATP
hydrolizes, the phosphate gets

00:03:35.320 --> 00:03:36.430
pulled off of it.

00:03:36.430 --> 00:03:39.330
This is an ATPase enzyme.

00:03:39.330 --> 00:03:40.320
That's what it does.

00:03:40.320 --> 00:03:41.570
Let me write that down.

00:03:54.250 --> 00:03:58.670
And what that does, that
releases the energy to cock

00:03:58.670 --> 00:04:03.030
this myosin protein into kind
of a high energy state.

00:04:03.030 --> 00:04:05.370
So let me do step two.

00:04:05.370 --> 00:04:08.310
This thing-- it gets
hydrolized.

00:04:08.310 --> 00:04:09.250
It releases energy.

00:04:09.250 --> 00:04:13.500
We know that ATP is the energy
currency of biological

00:04:13.500 --> 00:04:17.290
systems. So it releases
energy.

00:04:17.290 --> 00:04:19.579
I'm drawing it as a little spark
or explosion, but you

00:04:19.579 --> 00:04:23.010
can really imagine it's changing
the conformation of--

00:04:23.010 --> 00:04:26.540
it kind of spring-loads this
protein right here to go into

00:04:26.540 --> 00:04:29.750
a state so it's ready to
crawl along the myosin.

00:04:29.750 --> 00:04:36.500
So in step two-- plus energy,
energy and then this-- you can

00:04:36.500 --> 00:04:44.500
say it cocks the myosin
protein or

00:04:44.500 --> 00:04:47.410
enzyme to high energy.

00:04:47.410 --> 00:04:50.940
You can imagine it winds the
spring, or loads the spring.

00:04:57.650 --> 00:05:01.820
And conformation for proteins
just mean shape.

00:05:01.820 --> 00:05:05.970
So step two-- what happens is
the phosphate group gets--

00:05:05.970 --> 00:05:08.830
they're still attached, but
it gets detached from

00:05:08.830 --> 00:05:09.950
the rest of the ATP.

00:05:09.950 --> 00:05:12.770
So that becomes ADP and that
energy changes the

00:05:12.770 --> 00:05:16.420
conformation so that this
protein now goes into a

00:05:16.420 --> 00:05:19.230
position that looks like this.

00:05:19.230 --> 00:05:23.545
So this is where we end up
at the end of step two.

00:05:23.545 --> 00:05:27.490
Let me make sure
I do it right.

00:05:27.490 --> 00:05:29.130
So at the end of step
two, it might look

00:05:29.130 --> 00:05:30.380
something like this.

00:05:36.860 --> 00:05:39.930
So the end of step two,
the protein looks

00:05:39.930 --> 00:05:40.560
something like this.

00:05:40.560 --> 00:05:42.260
This is in its cocked
position.

00:05:42.260 --> 00:05:43.670
It has a lot of energy
right now.

00:05:43.670 --> 00:05:46.620
It's wound up in
this position.

00:05:46.620 --> 00:05:49.500
You still have your ADP.

00:05:49.500 --> 00:05:52.810
You still have your-- that's
your adenosine and let's say

00:05:52.810 --> 00:05:56.780
you have your two phosphate
groups on the ADP and you

00:05:56.780 --> 00:06:00.560
still have one phosphate
group right there.

00:06:00.560 --> 00:06:04.490
Now, when that phosphate group
releases-- so let me write

00:06:04.490 --> 00:06:06.040
this as step three.

00:06:06.040 --> 00:06:08.380
Remember, when we started, we
were just sitting here.

00:06:08.380 --> 00:06:12.190
The ATP binds on step one--
actually, it does definitely

00:06:12.190 --> 00:06:16.440
bind, at the end of step one,
that causes the myosin protein

00:06:16.440 --> 00:06:17.880
to get released.

00:06:17.880 --> 00:06:22.060
Then after step one, we
naturally have step two.

00:06:22.060 --> 00:06:25.470
The ATP hydrolyzes into
ADP phosphate.

00:06:25.470 --> 00:06:29.850
That releases energy and that
allows the myosin protein to

00:06:29.850 --> 00:06:33.230
get cocked into this high energy
position and kind of

00:06:33.230 --> 00:06:37.620
attach, you can think of
it, to the next rung

00:06:37.620 --> 00:06:39.480
of our actin filament.

00:06:39.480 --> 00:06:42.965
Now we're in a high
energy state.

00:06:47.160 --> 00:06:49.700
In step three, the phosphate
releases.

00:06:57.750 --> 00:07:01.980
The phosphate is released from
myosin in step three.

00:07:01.980 --> 00:07:03.170
That's step three right there.

00:07:03.170 --> 00:07:05.260
That's a phosphate group
being released.

00:07:05.260 --> 00:07:08.320
And what this does is, this
releases that energy of that

00:07:08.320 --> 00:07:14.150
cocked position and it causes
this myosin protein

00:07:14.150 --> 00:07:16.290
to push on the actin.

00:07:16.290 --> 00:07:18.730
This is the power stroke, if
you imagine in an engine.

00:07:18.730 --> 00:07:21.070
This is what's causing the
mechanical movement.

00:07:21.070 --> 00:07:23.390
So when the phosphate group is
actually released-- remember,

00:07:23.390 --> 00:07:25.470
the original release
is when you take

00:07:25.470 --> 00:07:27.430
ATP to ADP in a phosphate.

00:07:27.430 --> 00:07:30.030
That put it in this
spring-loaded position.

00:07:30.030 --> 00:07:32.925
When the phosphate releases it,
this releases the spring.

00:07:41.090 --> 00:07:43.430
And what that does is it pushes
on the actin filament.

00:07:49.930 --> 00:07:51.720
So you could view this
as the power stroke.

00:07:51.720 --> 00:07:53.750
We're actually creating
mechanical energy.

00:07:53.750 --> 00:07:56.130
So depending on which one you
want to view as fixed-- if you

00:07:56.130 --> 00:07:58.930
view the actin as fixed,
whatever myosin is attached to

00:07:58.930 --> 00:08:00.360
it would move to the left.

00:08:00.360 --> 00:08:04.530
If you imagine the myosin being
fixed, the actin and

00:08:04.530 --> 00:08:07.190
whatever it's attached to
would move to the right,

00:08:07.190 --> 00:08:07.900
either way.

00:08:07.900 --> 00:08:09.540
But this is where
we fundamentally

00:08:09.540 --> 00:08:10.950
get the muscle action.

00:08:10.950 --> 00:08:16.295
And then step four-- you
have the ADP released.

00:08:21.170 --> 00:08:25.960
And then we're exactly where
we were before we did step

00:08:25.960 --> 00:08:29.260
one, except we're just one rung
further to the left on

00:08:29.260 --> 00:08:31.890
the actin molecule.

00:08:31.890 --> 00:08:33.530
So to me, this is
pretty amazing.

00:08:33.530 --> 00:08:38.000
We actually are seeing how ATP
energy can be used to-- we're

00:08:38.000 --> 00:08:47.570
going from chemical energy
or bond energy in ATP to

00:08:47.570 --> 00:08:48.820
mechanical energy.

00:08:53.060 --> 00:08:55.080
For me, that's amazing because
when I first learned about

00:08:55.080 --> 00:08:58.640
ATP-- people say, you use ATP to
do everything in your cells

00:08:58.640 --> 00:08:59.650
and contract muscles.

00:08:59.650 --> 00:09:02.350
Well, gee, how do you go from
bond energy to actually

00:09:02.350 --> 00:09:04.850
contracting things, to actually
doing what we see in

00:09:04.850 --> 00:09:07.010
our everyday world as
mechanical energy?

00:09:07.010 --> 00:09:09.390
And this is really where
it all occurs.

00:09:09.390 --> 00:09:12.140
This is really the core issue
that's going on here.

00:09:12.140 --> 00:09:14.110
And you have to say, well, gee,
how this thing change

00:09:14.110 --> 00:09:15.290
shape and all that?

00:09:15.290 --> 00:09:17.320
And you have to remember,
these proteins, based on

00:09:17.320 --> 00:09:19.240
what's bonded to it and
what's not bonded to

00:09:19.240 --> 00:09:20.260
it, they change shape.

00:09:20.260 --> 00:09:23.810
And some of those shapes take
more energy to attain, and

00:09:23.810 --> 00:09:26.610
then if you do the right things,
that energy can be

00:09:26.610 --> 00:09:29.440
released and then it can
push another protein.

00:09:29.440 --> 00:09:30.920
But I find this just
fascinating.

00:09:30.920 --> 00:09:34.100
And now we can build up from
this actin and myosin

00:09:34.100 --> 00:09:37.930
interactions to understand how
muscles actually work.


Salman Khan interview with NPR's All Things Considered on 12/28/2009

WEBVTT
Kind: captions
Language: en

00:00:00.500 --> 00:00:02.670
ANNOUNCER: Is Carl
Kasell your friend?

00:00:02.670 --> 00:00:08.816
Find him and other NPR
folks at npr.org/community.

00:00:08.816 --> 00:00:10.190
ROBERT SIEGEL:
From NPR News this

00:00:10.190 --> 00:00:11.314
is "All Things Considered."

00:00:11.314 --> 00:00:14.390
I'm Robert Siegel, and it's time
now for All Tech Considered.

00:00:20.760 --> 00:00:23.650
These days, you can
learn just about anything

00:00:23.650 --> 00:00:24.650
from a YouTube video.

00:00:24.650 --> 00:00:25.150
[PLAYBACK]

00:00:25.150 --> 00:00:26.774
SPEAKER 1: First of
all, we want to put

00:00:26.774 --> 00:00:27.960
this bow around his neck.

00:00:27.960 --> 00:00:28.280
[END PLAYBACK]

00:00:28.280 --> 00:00:29.420
ROBERT SIEGEL: A
South Carolina man

00:00:29.420 --> 00:00:31.070
teaches us how to tie a bow tie.

00:00:31.070 --> 00:00:35.499
His YouTube video has been
viewed more than 650,000 times.

00:00:35.499 --> 00:00:38.040
Or maybe you've always wanted
to learn how to play the piano.

00:00:38.040 --> 00:00:38.232
[PLAYBACK]

00:00:38.232 --> 00:00:38.810
[PIANO CHORD]

00:00:38.810 --> 00:00:40.851
SPEAKER 2: Let's make this
thing minor, shall we?

00:00:40.851 --> 00:00:42.856
We take the middle
finger and move it

00:00:42.856 --> 00:00:44.141
down a half step to the F.

00:00:44.141 --> 00:00:44.682
[PIANO CHORD]

00:00:44.682 --> 00:00:45.130
[END PLAYBACK]

00:00:45.130 --> 00:00:46.240
ROBERT SIEGEL: Today
on All Tech Considered,

00:00:46.240 --> 00:00:47.656
we're going to
talk with a man who

00:00:47.656 --> 00:00:50.920
is devoting his life to
creating YouTube tutorials.

00:00:50.920 --> 00:00:51.420
[PLAYBACK]

00:00:51.420 --> 00:00:52.570
SALMAN KHAN: Welcome
to the presentation

00:00:52.570 --> 00:00:54.090
on multiplying fractions.

00:00:54.090 --> 00:00:57.040
Today you'll be very happy
because you'll find out

00:00:57.040 --> 00:00:58.860
that this is one of
the few times where

00:00:58.860 --> 00:01:02.050
multiplying something is
easier than adding it.

00:01:02.050 --> 00:01:04.175
And if you don't believe
me let's do some problems.

00:01:04.175 --> 00:01:04.530
[END PLAYBACK]

00:01:04.530 --> 00:01:06.200
ROBERT SIEGEL: That
is Salman Khan.

00:01:06.200 --> 00:01:08.650
Not the Salman Khan
who's a Bollywood star.

00:01:08.650 --> 00:01:11.300
This is the Salman Khan,
former hedge fund analyst

00:01:11.300 --> 00:01:12.810
turned online tutor.

00:01:12.810 --> 00:01:15.830
He has produced more than
1,000 YouTube videos, ranging

00:01:15.830 --> 00:01:18.360
from basic multiplication
of fractions

00:01:18.360 --> 00:01:20.780
to polynomial
approximation of functions.

00:01:20.780 --> 00:01:23.200
And he joins us now from
Silicon Valley in California.

00:01:23.200 --> 00:01:23.530
Welcome.

00:01:23.530 --> 00:01:24.160
SALMAN KHAN: Thanks.

00:01:24.160 --> 00:01:25.743
ROBERT SIEGEL: Your
channel on YouTube

00:01:25.743 --> 00:01:27.830
is called the "Khan
Academy Channel."

00:01:27.830 --> 00:01:31.170
Why did you decide to
become a tutor online?

00:01:31.170 --> 00:01:33.320
SALMAN KHAN: It happened
fairly organically.

00:01:33.320 --> 00:01:36.920
I started remotely tutoring some
of my cousins in New Orleans.

00:01:36.920 --> 00:01:39.340
I was working, as you mentioned,
as a hedge fund analyst

00:01:39.340 --> 00:01:40.760
in Boston at the time.

00:01:40.760 --> 00:01:42.900
My cousin Nadia
was having trouble

00:01:42.900 --> 00:01:44.574
placing into the
pre-algebra class.

00:01:44.574 --> 00:01:45.990
So I talked to
Nadia a little bit.

00:01:45.990 --> 00:01:48.904
And I said, how about you and
me do some remote tutoring

00:01:48.904 --> 00:01:51.320
after I come home from work
and you come home from school.

00:01:51.320 --> 00:01:52.984
We'll get a
conference call going,

00:01:52.984 --> 00:01:54.525
and maybe we'll use
Instant Messenger

00:01:54.525 --> 00:01:55.733
or we'll find something else.

00:01:55.733 --> 00:01:57.600
We ended up using Yahoo Doodle.

00:01:57.600 --> 00:01:59.890
And word got around
amongst friends and family,

00:01:59.890 --> 00:02:02.274
and I had a little cohort
of about 10 or 15 students.

00:02:02.274 --> 00:02:04.190
And then it just became
difficult logistically

00:02:04.190 --> 00:02:06.770
between my work and
their soccer practice.

00:02:06.770 --> 00:02:09.370
And I had to keep tutoring
the same lessons over and over

00:02:09.370 --> 00:02:11.330
again depending on
how old they were,

00:02:11.330 --> 00:02:14.577
so I decided to just record my
lessons but in the same style

00:02:14.577 --> 00:02:16.910
that I was doing with Nadia
that seemed to be effective.

00:02:16.910 --> 00:02:18.170
And I started just recording
them and putting them

00:02:18.170 --> 00:02:19.050
on YouTube.

00:02:19.050 --> 00:02:20.950
And even your or my
great-great-grandkids

00:02:20.950 --> 00:02:22.760
could learn from
these same videos.

00:02:22.760 --> 00:02:24.718
ROBERT SIEGEL: Now, I've
watched a few of them.

00:02:24.718 --> 00:02:27.390
You never appear on
screen, just a mouse

00:02:27.390 --> 00:02:30.220
arrow that draws in different
colors on a black background.

00:02:30.220 --> 00:02:31.250
And you narrate.

00:02:31.250 --> 00:02:32.840
How are you actually
making these?

00:02:32.840 --> 00:02:34.630
SALMAN KHAN: When
I started, it was

00:02:34.630 --> 00:02:36.880
literallY-- I took
Microsoft Paint, made

00:02:36.880 --> 00:02:39.260
the background black, picked
some florescent colors,

00:02:39.260 --> 00:02:41.349
and I used this
shareware-- I think

00:02:41.349 --> 00:02:42.890
it was called Screen
Video Recorders,

00:02:42.890 --> 00:02:46.300
it was a $20 piece of
software-- to capture my screen

00:02:46.300 --> 00:02:48.040
and to record my voice
at the same time.

00:02:48.040 --> 00:02:49.080
And that would just
produce the videos.

00:02:49.080 --> 00:02:50.900
I just did it because
that was, I thought,

00:02:50.900 --> 00:02:54.050
the cheapest and fastest way
to make a decent quality video.

00:02:54.050 --> 00:02:55.840
Since then, one of
the viewers actually

00:02:55.840 --> 00:02:58.140
donated a $300 piece
of software called

00:02:58.140 --> 00:03:00.680
Camtasia Recorder for
the screen capture.

00:03:00.680 --> 00:03:04.360
And now I use another piece of
shareware called Smooth Draw 2,

00:03:04.360 --> 00:03:05.430
I think it's called.

00:03:05.430 --> 00:03:06.700
I use that to draw.

00:03:06.700 --> 00:03:10.070
And I just have a little
Wacom graphic pen tablet

00:03:10.070 --> 00:03:11.230
to do the writing.

00:03:11.230 --> 00:03:12.060
ROBERT SIEGEL: Now
let's go through some

00:03:12.060 --> 00:03:13.880
of the range of what
you're doing tutorials

00:03:13.880 --> 00:03:17.156
in, in mathematics and
chemistry, biology.

00:03:17.156 --> 00:03:18.780
SALMAN KHAN: Yeah,
in the non-sciences,

00:03:18.780 --> 00:03:21.297
there's obviously a lot
on finance and economics.

00:03:21.297 --> 00:03:23.130
Actually, a lot of that
comes from last year

00:03:23.130 --> 00:03:24.600
during the financial crisis.

00:03:24.600 --> 00:03:27.074
In my hedge fund world, I
put all my money in cash

00:03:27.074 --> 00:03:28.990
and I started reading
the Federal Reserve Act.

00:03:28.990 --> 00:03:31.606
I read it about 10 times just
to understand all of the levers

00:03:31.606 --> 00:03:33.480
that the Federal Reserve
Chairman could pull.

00:03:33.480 --> 00:03:34.560
And I said, well,
what's a better

00:03:34.560 --> 00:03:36.600
use of my time than
whatever I just learned.

00:03:36.600 --> 00:03:38.400
Let me make a series
of YouTube videos

00:03:38.400 --> 00:03:40.620
on fractional reserve banking
in the Federal Reserve.

00:03:40.620 --> 00:03:42.160
And I don't plan
on limiting myself

00:03:42.160 --> 00:03:43.672
to just the maths
and the sciences

00:03:43.672 --> 00:03:45.130
ROBERT SIEGEL: Now
here's something

00:03:45.130 --> 00:03:48.510
I noticed while
watching a tutorial

00:03:48.510 --> 00:03:50.710
you were giving about stocks.

00:03:50.710 --> 00:03:52.620
You were, I think,
making the point

00:03:52.620 --> 00:03:55.830
that a stock that
costs $1 a share

00:03:55.830 --> 00:03:59.440
is not necessarily cheaper than
a stock that costs $10 a share.

00:03:59.440 --> 00:04:01.600
As I'm watching
it, a crawl comes

00:04:01.600 --> 00:04:04.890
across the bottom from
Google directing me

00:04:04.890 --> 00:04:06.420
to a website where
I can look over

00:04:06.420 --> 00:04:08.215
the prospectus for
various penny stocks.

00:04:08.215 --> 00:04:10.340
It's an advertisement, and
indeed the advertisement

00:04:10.340 --> 00:04:13.067
is actually based
on a proposition

00:04:13.067 --> 00:04:15.400
that you're shooting down in
the course of the tutorial.

00:04:15.400 --> 00:04:15.899
SALMAN KHAN: [LAUGHING]

00:04:15.899 --> 00:04:17.850
ROBERT SIEGEL: So
who's advertising?

00:04:17.850 --> 00:04:19.940
How many of your
courses are advertised?

00:04:19.940 --> 00:04:23.470
And how do you feel about
this kind of education

00:04:23.470 --> 00:04:25.180
being underwritten by a sponsor?

00:04:25.180 --> 00:04:28.050
SALMAN KHAN: The advertising
is what YouTube puts up just

00:04:28.050 --> 00:04:29.890
by virtue of it
being on YouTube.

00:04:29.890 --> 00:04:32.040
I do share some of the revenue.

00:04:32.040 --> 00:04:36.310
It was pushing about $1,500 of
revenue to Khan Academy Inc,

00:04:36.310 --> 00:04:38.937
which is a 501(c)(3)
not-for-profit organization.

00:04:38.937 --> 00:04:40.770
So it's going to the
organization right now.

00:04:40.770 --> 00:04:43.779
It's not coming to me as
a salary anyway right now.

00:04:43.779 --> 00:04:45.820
ROBERT SIEGEL: Without
the advertising, are you--

00:04:45.820 --> 00:04:48.194
I know you were working for
a hedge fund before-- but are

00:04:48.194 --> 00:04:49.760
you-- is this self-sustaining?

00:04:49.760 --> 00:04:54.270
Can you support this as a
career doing it based on people

00:04:54.270 --> 00:04:56.170
free of charge
looking at videos?

00:04:56.170 --> 00:04:58.950
SALMAN KHAN: Well right now,
it isn't self-sustaining

00:04:58.950 --> 00:04:59.910
as of today.

00:04:59.910 --> 00:05:02.680
I joke that it's being
funded by the Salman Khan

00:05:02.680 --> 00:05:04.380
Bank Of America
checking account.

00:05:04.380 --> 00:05:07.900
My wife has given me a year
to make it self-sustaining,

00:05:07.900 --> 00:05:10.690
although I think she'll give me
a little more leeway than that.

00:05:10.690 --> 00:05:12.946
If I get no outside
support, there

00:05:12.946 --> 00:05:14.320
are the donations
that are coming

00:05:14.320 --> 00:05:16.410
in from the viewers themselves.

00:05:16.410 --> 00:05:20.600
That's bringing in
about $1,500 a month.

00:05:20.600 --> 00:05:22.406
I have these kind of
low-key ads that you

00:05:22.406 --> 00:05:24.030
mentioned that are
just off of YouTube.

00:05:24.030 --> 00:05:26.280
If I were to be aggressive
with the advertising, which

00:05:26.280 --> 00:05:28.410
I don't want to do,
I could probably

00:05:28.410 --> 00:05:30.640
generate another few
thousand dollars a month.

00:05:30.640 --> 00:05:32.690
And at the rate that the
viewership is growing--

00:05:32.690 --> 00:05:35.390
it's growing at about
15% or 20% per month--

00:05:35.390 --> 00:05:38.450
I'm reasonably confident
that in about a year the site

00:05:38.450 --> 00:05:40.800
itself could pay my rent
and put food on the table.

00:05:40.800 --> 00:05:43.860
ROBERT SIEGEL: Are you a faculty
of one at the Khan Academy?

00:05:43.860 --> 00:05:45.300
SALMAN KHAN: I currently am.

00:05:45.300 --> 00:05:47.510
There are people who have
come out of the woodworks

00:05:47.510 --> 00:05:49.440
really in the last
two months or so

00:05:49.440 --> 00:05:51.077
to volunteer
translating the videos.

00:05:51.077 --> 00:05:52.660
There's a chemistry
teacher in Uruguay

00:05:52.660 --> 00:05:54.350
who did the first translation.

00:05:54.350 --> 00:05:57.000
There's an effort going on
to translate into Arabic,

00:05:57.000 --> 00:06:00.450
into Polish, into
Portuguese, into German,

00:06:00.450 --> 00:06:02.180
but right now all
of the content is

00:06:02.180 --> 00:06:03.825
and has been generated by me.

00:06:03.825 --> 00:06:05.980
ROBERT SIEGEL: You come
across in these videos

00:06:05.980 --> 00:06:07.950
as a very natural teacher.

00:06:07.950 --> 00:06:11.687
And I wonder, on the way
through MIT and Harvard Business

00:06:11.687 --> 00:06:13.770
School and the hedge fund
trade, did you ever just

00:06:13.770 --> 00:06:15.240
consider becoming a teacher?

00:06:15.240 --> 00:06:17.100
SALMAN KHAN: I actually
was a teacher just

00:06:17.100 --> 00:06:18.955
to make some extra
cash during college.

00:06:18.955 --> 00:06:21.900
I was an MCAT instructor
for the Princeton Review

00:06:21.900 --> 00:06:24.260
for one summer, and
I used to a volunteer

00:06:24.260 --> 00:06:26.450
teaching middle school
kids at the Devotion

00:06:26.450 --> 00:06:27.720
School in Brookline.

00:06:27.720 --> 00:06:29.570
It's something that
I really enjoy,

00:06:29.570 --> 00:06:32.760
but the economics of
the hedge fund world

00:06:32.760 --> 00:06:34.585
were a little bit better.

00:06:34.585 --> 00:06:36.960
ROBERT SIEGEL: You could have
done a very simple tutorial

00:06:36.960 --> 00:06:40.690
on the difference between
the pay of a hedge fund

00:06:40.690 --> 00:06:43.060
analyst and a teacher.

00:06:43.060 --> 00:06:44.560
When you're teaching
online, there's

00:06:44.560 --> 00:06:47.100
not a real-time exchange
with the students,

00:06:47.100 --> 00:06:50.090
and their comments to you
aren't coming back in real time.

00:06:50.090 --> 00:06:54.760
Do you think that would be
an added virtue of education,

00:06:54.760 --> 00:06:56.205
or does it matter that much?

00:06:56.205 --> 00:06:57.580
SALMAN KHAN: I
think that this is

00:06:57.580 --> 00:07:00.990
an advantage I have over
a traditional teacher,

00:07:00.990 --> 00:07:04.007
just from my limited
experience from teaching live.

00:07:04.007 --> 00:07:05.465
One of the hardest
things is to sit

00:07:05.465 --> 00:07:08.140
in front of a classroom
of 20 to 30 students,

00:07:08.140 --> 00:07:10.569
and maybe five of them are
giving you a nice attentive

00:07:10.569 --> 00:07:12.610
expression and the rest
of them have blank faces.

00:07:12.610 --> 00:07:14.880
You don't know if they're bored
or they're falling behind.

00:07:14.880 --> 00:07:17.255
It makes you insecure and you
don't know what to do next.

00:07:17.255 --> 00:07:19.470
But I go to my computer,
spend 10 minutes,

00:07:19.470 --> 00:07:22.900
explain something as I would
explain it to you or my cousin,

00:07:22.900 --> 00:07:24.770
and then I upload it on YouTube.

00:07:24.770 --> 00:07:27.180
The whole process takes
maybe half an hour.

00:07:27.180 --> 00:07:28.930
And within an hour of
putting up a video,

00:07:28.930 --> 00:07:30.700
a few hundred people
will watch it.

00:07:30.700 --> 00:07:34.540
And I wait for them to give
that YouTube five-star rating

00:07:34.540 --> 00:07:37.240
and put a couple of comments up
saying, oh, this is so great.

00:07:37.240 --> 00:07:38.670
I was going to fail this class.

00:07:38.670 --> 00:07:40.961
Now I'm going to pass the
exam tomorrow, whatever else.

00:07:40.961 --> 00:07:43.510
So I wait for that
feedback, and that gives me

00:07:43.510 --> 00:07:44.970
the confidence to keep going.

00:07:44.970 --> 00:07:47.790
ROBERT SIEGEL: Salman Khan, who
teaches math, science, finance,

00:07:47.790 --> 00:07:49.580
and much more at
khanacademy.org.

00:07:52.404 --> 00:07:54.070
Thank you very much
for talking with us.

00:07:54.070 --> 00:07:56.050
SALMAN KHAN: Thank
you very much.


Neuronal synapses (chemical)

WEBVTT
Kind: captions
Language: en

00:00:00.670 --> 00:00:04.040
I think we have a decent idea of
how a signal is transmitted

00:00:04.040 --> 00:00:05.620
along the neuron.

00:00:05.620 --> 00:00:08.800
We saw that a couple of
dendrites, maybe that one and

00:00:08.800 --> 00:00:13.000
that one and that one, might
get excited or triggered.

00:00:13.000 --> 00:00:14.960
And when we say it gets
triggered, we're saying that

00:00:14.960 --> 00:00:16.800
some type of channel
gets opened.

00:00:16.800 --> 00:00:18.290
That's probably the trigger.

00:00:18.290 --> 00:00:22.790
That channel allows ions to be
released into the cell-- or

00:00:22.790 --> 00:00:25.120
actually, there are situations
where ions can be released out

00:00:25.120 --> 00:00:25.550
of the cell.

00:00:25.550 --> 00:00:27.700
It would be inhibitory, but
let's take the case where ions

00:00:27.700 --> 00:00:31.820
are released into the cells in
an electrotonic fashion.

00:00:31.820 --> 00:00:35.510
It changes the charge or the
voltage gradient across the

00:00:35.510 --> 00:00:38.750
membrane and if the combined
effects of the change in the

00:00:38.750 --> 00:00:42.280
voltage gradient is just enough
at the axon hillock to

00:00:42.280 --> 00:00:46.790
meet that threshold, then the
sodium channels over here will

00:00:46.790 --> 00:00:51.030
open up, sodium floods in, and
then we have the situation

00:00:51.030 --> 00:00:54.160
where the voltage becomes
very positive.

00:00:54.160 --> 00:00:57.090
Potassium channels open up to
change things again, but by

00:00:57.090 --> 00:00:59.710
the time we went very
positive, then that

00:00:59.710 --> 00:01:03.320
eletrotonically affects
the next sodium pump.

00:01:03.320 --> 00:01:06.730
But then we have the situation
where that will allow sodium

00:01:06.730 --> 00:01:09.360
ions to flood in and then
the signal keeps getting

00:01:09.360 --> 00:01:10.550
transmitted.

00:01:10.550 --> 00:01:15.240
Now the next natural question
is, what happens at the neuron

00:01:15.240 --> 00:01:17.590
to neuron junctions?

00:01:17.590 --> 00:01:19.640
We said that this dendrite gets

00:01:19.640 --> 00:01:21.550
triggered or gets excited.

00:01:21.550 --> 00:01:24.050
In most cases, it's getting
triggered or excited by

00:01:24.050 --> 00:01:24.810
another neuron.

00:01:24.810 --> 00:01:26.340
It could be something else.

00:01:26.340 --> 00:01:31.550
And over here, when this axon
fires, it should be exciting

00:01:31.550 --> 00:01:32.520
either another cell.

00:01:32.520 --> 00:01:35.760
It could be a muscle cell or--
in probably most cases of the

00:01:35.760 --> 00:01:39.820
human body-- it's exciting
another neuron.

00:01:39.820 --> 00:01:41.050
And so how does it do that?

00:01:41.050 --> 00:01:43.140
So this is the terminal
end of the axon.

00:01:43.140 --> 00:01:46.535
There could be the dendrite of
another neuron right here.

00:01:51.910 --> 00:01:55.430
This is another neuron with its
own axon, its own cell.

00:01:55.430 --> 00:01:58.400
This would trigger the
dendrite right there.

00:01:58.400 --> 00:02:00.190
So the question is, how
does that happen?

00:02:00.190 --> 00:02:04.130
How does the signal go from one
neuron's axon to the next

00:02:04.130 --> 00:02:04.990
neuron's dendrite?

00:02:04.990 --> 00:02:07.770
It actually always doesn't
have to go from axon to

00:02:07.770 --> 00:02:09.449
dendrite, but that's
the most typical.

00:02:09.449 --> 00:02:12.460
You can actually go from axon to
axon, dendrite to dendrite,

00:02:12.460 --> 00:02:16.040
axon to soma-- but let's just
focus on axon to dendrite

00:02:16.040 --> 00:02:19.340
because that's the most
traditional way that neurons

00:02:19.340 --> 00:02:22.180
transmit information from
one to the other.

00:02:22.180 --> 00:02:22.990
So let's zoom in.

00:02:22.990 --> 00:02:24.700
Let's zoom in right here.

00:02:24.700 --> 00:02:27.610
This little box right there,
let's zoom at the base, the

00:02:27.610 --> 00:02:31.740
terminal end of this axon
and let's zoom in

00:02:31.740 --> 00:02:33.020
on this whole area.

00:02:33.020 --> 00:02:35.010
Then we'll also zoom in-- we're
also going to get the

00:02:35.010 --> 00:02:37.370
dendrite of this next neuron--
and I'm going to rotate it.

00:02:37.370 --> 00:02:39.320
Actually, I don't even
have to rotate it.

00:02:39.320 --> 00:02:42.950
So to do that, let me draw
the terminal end.

00:02:42.950 --> 00:02:45.090
So let's say the terminal end
looks something like this.

00:02:45.090 --> 00:02:47.215
I'm zoomed in big time.

00:02:49.900 --> 00:02:52.090
This is the terminal
end of the neuron.

00:02:52.090 --> 00:02:58.160
This is inside the neuron and
then the next dendrite-- let

00:02:58.160 --> 00:02:59.485
me draw it right here.

00:03:06.280 --> 00:03:07.800
So we've really zoomed in.

00:03:07.800 --> 00:03:17.100
So this is the dendrite
of the next neuron.

00:03:17.100 --> 00:03:19.710
This is inside the
first neuron.

00:03:19.710 --> 00:03:22.080
So we have this action
potential that

00:03:22.080 --> 00:03:23.640
keeps traveling along.

00:03:23.640 --> 00:03:27.580
Eventually for maybe right over
here-- I don't know if

00:03:27.580 --> 00:03:30.970
you can zoom in-- which would
be over here, the action

00:03:30.970 --> 00:03:34.680
potential makes the electrical
potential or the voltage

00:03:34.680 --> 00:03:38.480
potential across this membrane
just positive enough to

00:03:38.480 --> 00:03:42.410
trigger this sodium channel.

00:03:42.410 --> 00:03:47.610
So actually, maybe
I'm really close.

00:03:47.610 --> 00:03:49.750
This channel is this
one right here.

00:03:49.750 --> 00:03:53.340
So then it allows a flood of
sodium to enter the cell.

00:03:56.110 --> 00:03:57.560
And then the the whole
thing happens.

00:03:57.560 --> 00:03:59.780
You have potassium that can then
take it out, but by the

00:03:59.780 --> 00:04:03.340
time this comes in, this
positive charge, it can

00:04:03.340 --> 00:04:06.930
trigger another channel and it
could trigger another sodium

00:04:06.930 --> 00:04:09.240
channel if there's other sodium
channels further down,

00:04:09.240 --> 00:04:11.750
but near the end of
the axon there are

00:04:11.750 --> 00:04:15.470
actually calcium channels.

00:04:15.470 --> 00:04:17.200
I'll do that in pink.

00:04:17.200 --> 00:04:23.680
So this is a calcium channel
that is traditionally closed.

00:04:23.680 --> 00:04:25.960
So this is a calcium
ion channel.

00:04:25.960 --> 00:04:27.545
Calcium has a plus 2 charge.

00:04:30.070 --> 00:04:33.230
It tends to be closed, but
it's also voltage gated.

00:04:33.230 --> 00:04:37.960
When the voltage gets high
enough, it's very similar to a

00:04:37.960 --> 00:04:41.670
sodium voltage gated channel is
that if it becomes positive

00:04:41.670 --> 00:04:45.640
enough near the gate, it will
open up and when it opens up,

00:04:45.640 --> 00:04:49.400
it allows calcium ions to
flood into the cell.

00:04:49.400 --> 00:04:53.450
So the calcium ions, their
plus 2 charge, to

00:04:53.450 --> 00:04:55.180
flood into the cells.

00:04:55.180 --> 00:04:58.270
Now you're saying, hey Sal, why
are calcium ions flooding

00:04:58.270 --> 00:04:58.980
into the cells?

00:04:58.980 --> 00:05:00.660
These have positive charge.

00:05:00.660 --> 00:05:03.530
I just thought you said that the
cell is becoming positive

00:05:03.530 --> 00:05:05.130
because of all the sodium
flowing in.

00:05:05.130 --> 00:05:07.300
Why would this calcium
want to flow in?

00:05:07.300 --> 00:05:09.890
And the reason why it wants to
flow in is because the cell

00:05:09.890 --> 00:05:14.940
also-- just like it pumps out
sodium and pumps in potassium,

00:05:14.940 --> 00:05:19.990
the cell also has calcium ion
pumps and the mechanism is

00:05:19.990 --> 00:05:23.120
nearly identical to what I
showed you on the sodium

00:05:23.120 --> 00:05:26.090
potassium pump, but it just
deals with calcium.

00:05:26.090 --> 00:05:30.550
So you literally have these
proteins that are sitting

00:05:30.550 --> 00:05:31.820
across the membrane.

00:05:31.820 --> 00:05:35.720
This is a phospobilipid
layer membrane.

00:05:35.720 --> 00:05:38.560
Maybe I'll draw two layers here
just so you realize it's

00:05:38.560 --> 00:05:41.470
a bi-layer membrane.

00:05:41.470 --> 00:05:42.525
Let me draw it like that.

00:05:42.525 --> 00:05:47.020
That makes it look a little bit
more realistic, although

00:05:47.020 --> 00:05:48.670
the whole thing is not
very realistic.

00:05:48.670 --> 00:05:52.776
And this is also going to
be a bilipid membrane.

00:05:52.776 --> 00:05:56.660
You get the idea, but
let me just do it to

00:05:56.660 --> 00:05:59.400
make the point clear.

00:05:59.400 --> 00:06:02.620
So there are also these calcium
ion pumps that are

00:06:02.620 --> 00:06:07.100
also subsets of ATPases, which
they're just like the sodium

00:06:07.100 --> 00:06:08.180
potassium pumps.

00:06:08.180 --> 00:06:13.720
You give them one ATP and a
calcium will bond someplace

00:06:13.720 --> 00:06:20.240
else and it'll pull apart the
phosphate from the ATP and

00:06:20.240 --> 00:06:22.950
that'll be enough energy to
change the confirmation of

00:06:22.950 --> 00:06:25.720
this protein and it'll
push the calcium out.

00:06:25.720 --> 00:06:29.040
Essentially, what was the
calcium will bond and then

00:06:29.040 --> 00:06:33.500
it'll open up so the calcium
can only exit the cell.

00:06:33.500 --> 00:06:36.350
It's just like the sodium
potassium pumps, but it's good

00:06:36.350 --> 00:06:38.880
to know in the resting state,
you have a high concentration

00:06:38.880 --> 00:06:42.200
of calcium ions out here and
it's all driven by ATP.

00:06:42.200 --> 00:06:45.170
A much higher concentration on
the outside than you have on

00:06:45.170 --> 00:06:47.870
the inside and it's driven
by those ion pumps.

00:06:47.870 --> 00:06:50.980
So once you have this action
potential, instead of

00:06:50.980 --> 00:06:54.360
triggering another sodium gate,
it starts triggering

00:06:54.360 --> 00:06:58.630
calcium gates and these calcium
ions flood into the

00:06:58.630 --> 00:07:01.190
terminal end of this axon.

00:07:01.190 --> 00:07:05.810
Now, these calcium ions, they
bond to other proteins.

00:07:05.810 --> 00:07:07.980
And before I go to those other
proteins, we have to keep in

00:07:07.980 --> 00:07:12.230
mind what's going on near this
junction right here.

00:07:12.230 --> 00:07:14.840
And I've used the word
synapse already--

00:07:14.840 --> 00:07:16.100
actually, maybe I haven't.

00:07:16.100 --> 00:07:21.240
The place where this axon is
meeting with this dendrite,

00:07:21.240 --> 00:07:22.490
this is the synapse.

00:07:29.060 --> 00:07:31.680
Or you can kind of view it as
the touching point or the

00:07:31.680 --> 00:07:34.020
communication point or
the connection point.

00:07:34.020 --> 00:07:37.480
And this neuron right
here, this is called

00:07:37.480 --> 00:07:39.920
the presynaptic neuron.

00:07:39.920 --> 00:07:40.730
Let me write that down.

00:07:40.730 --> 00:07:42.660
It's good to have a little
terminology under our belt.

00:07:49.220 --> 00:07:51.250
This is the post-synaptic
neuron.

00:07:58.550 --> 00:08:02.740
And the space between the two
neurons, between this axon and

00:08:02.740 --> 00:08:05.680
this dendrite, this is called
the synaptic cleft.

00:08:12.610 --> 00:08:15.700
It's a really small space in the
terms of-- so what we're

00:08:15.700 --> 00:08:18.900
going to deal with in this video
is a chemical synapse.

00:08:18.900 --> 00:08:21.450
In general, when people talk
about synapses, they're

00:08:21.450 --> 00:08:23.260
talking about chemical
synapses.

00:08:23.260 --> 00:08:25.880
There also are electrical
synapses, but I won't go into

00:08:25.880 --> 00:08:26.810
detail on those.

00:08:26.810 --> 00:08:29.470
This is kind of the most
traditional one that people

00:08:29.470 --> 00:08:30.650
talk about.

00:08:30.650 --> 00:08:34.669
So your synaptic cleft in
chemical synapses is about 20

00:08:34.669 --> 00:08:38.460
nanometers, which
is really small.

00:08:38.460 --> 00:08:45.620
If you think about the average
width of a cell as about 10 to

00:08:45.620 --> 00:08:49.150
100 microns-- this micron
is 10 to the minus 6.

00:08:49.150 --> 00:08:52.160
This is 20 times 10 to
the minus 9 meters.

00:08:52.160 --> 00:08:54.290
So this is a very small distance
and it makes sense

00:08:54.290 --> 00:08:56.950
because look how big
the cells look next

00:08:56.950 --> 00:08:58.040
to this small distance.

00:08:58.040 --> 00:09:02.210
So it's a very small distance
and you have-- on the

00:09:02.210 --> 00:09:05.370
presynaptic neuron near
the terminal end,

00:09:05.370 --> 00:09:06.750
you have these vesicles.

00:09:06.750 --> 00:09:07.770
Remember what vesicles were.

00:09:07.770 --> 00:09:13.920
These are just membrane bound
things inside of the cell.

00:09:13.920 --> 00:09:16.120
So you have these vesicles.

00:09:16.120 --> 00:09:20.760
They also have their
phospobilipid layers, their

00:09:20.760 --> 00:09:21.360
little membranes.

00:09:21.360 --> 00:09:23.590
So you have these vesicles so
these are just-- you can kind

00:09:23.590 --> 00:09:25.350
of view them as containers.

00:09:25.350 --> 00:09:31.020
I'll just draw one more
just like that.

00:09:31.020 --> 00:09:34.060
And they can train these
molecules called

00:09:34.060 --> 00:09:36.520
neurotransmitters and
I'll draw the

00:09:36.520 --> 00:09:41.280
neurotransmitters in green.

00:09:41.280 --> 00:09:42.790
So they have these
molecules called

00:09:42.790 --> 00:09:45.140
neurotransmitters in them.

00:09:45.140 --> 00:09:48.410
You've probably heard
the word before.

00:09:48.410 --> 00:09:53.050
In fact, a lot of drugs that
people use for depression or

00:09:53.050 --> 00:09:59.380
other things related to our
mental state, they affect

00:09:59.380 --> 00:10:01.100
neurotransmitters.

00:10:01.100 --> 00:10:03.720
I won't go into detail there,
but they contain these

00:10:03.720 --> 00:10:04.710
neurotransmitters.

00:10:04.710 --> 00:10:08.810
And when the calcium channels--
they're voltage

00:10:08.810 --> 00:10:11.360
gated-- when it becomes a little
more positive, they

00:10:11.360 --> 00:10:15.310
open calcium floods in and what
the calcium does is, it

00:10:15.310 --> 00:10:19.820
bonds to these proteins that
have docked these vesciles.

00:10:19.820 --> 00:10:26.170
So these little vesicles,
they're docked to the

00:10:26.170 --> 00:10:30.430
presynpatic membrane or to this
axon terminal membrane

00:10:30.430 --> 00:10:30.820
right there.

00:10:30.820 --> 00:10:33.520
These proteins are actually
called SNARE proteins.

00:10:33.520 --> 00:10:36.290
It's an acronym, but it's also
a good word because they've

00:10:36.290 --> 00:10:39.540
literally snared the vesicles
to this membrane.

00:10:39.540 --> 00:10:41.470
So that's what these
proteins are.

00:10:41.470 --> 00:10:45.810
And when these calcium ions
flood in, they bond to these

00:10:45.810 --> 00:10:50.970
proteins, they attach to these
proteins, and they change the

00:10:50.970 --> 00:10:53.850
confirmation of the proteins
just enough that these

00:10:53.850 --> 00:11:00.610
proteins bring these vesicles
closer to the membrane and

00:11:00.610 --> 00:11:03.090
also kind of pull apart the
two membranes so that the

00:11:03.090 --> 00:11:04.040
membranes merge.

00:11:04.040 --> 00:11:07.180
Let me do a zoom in of that
just to make it clear

00:11:07.180 --> 00:11:08.370
what's going on.

00:11:08.370 --> 00:11:11.700
So after they've bonded-- this
is kind of before the calcium

00:11:11.700 --> 00:11:16.070
comes in, bonds to those SNARE
proteins, then the SNARE

00:11:16.070 --> 00:11:20.190
protein will bring the vesicle
ultra-close to

00:11:20.190 --> 00:11:22.580
the presynaptic membrane.

00:11:22.580 --> 00:11:25.710
So that's the vesicle and then
the presynaptic membrane will

00:11:25.710 --> 00:11:32.370
look like this and then you
have your SNARE proteins.

00:11:32.370 --> 00:11:34.560
And I'm not obviously drawing it
exactly how it looks in the

00:11:34.560 --> 00:11:37.210
cell, but it'll give you the
idea of what's going on.

00:11:37.210 --> 00:11:42.000
Your SNARE proteins have
essentially pulled the things

00:11:42.000 --> 00:11:44.510
together and have pulled them
apart so that these two

00:11:44.510 --> 00:11:45.780
membranes merge.

00:11:45.780 --> 00:11:48.050
And then the main side effect--
the reason why all

00:11:48.050 --> 00:11:51.350
this is happening-- is it allows
those neurotransmitters

00:11:51.350 --> 00:11:54.070
to be dumped into the
synaptic cleft.

00:11:54.070 --> 00:11:57.980
So those neurotransmitters
that were inside of our

00:11:57.980 --> 00:12:01.360
vesicle then get dumped into
the synaptic cleft.

00:12:04.840 --> 00:12:07.630
This process right here
is called exocytosis.

00:12:07.630 --> 00:12:12.170
It's exiting the cytoplasm,
you could say, of the

00:12:12.170 --> 00:12:14.210
presynaptic neuron.

00:12:14.210 --> 00:12:17.130
These neurotransmitters-- and
you've probably heard the

00:12:17.130 --> 00:12:20.560
specific names of many of
these-- serotonin, dopamine,

00:12:20.560 --> 00:12:23.770
epinephrine-- which is also
adrenaline, but that's also a

00:12:23.770 --> 00:12:26.130
hormone, but it also acts
as a neurotransmitter.

00:12:26.130 --> 00:12:29.380
Norepinephrine, also both
a hormone and a

00:12:29.380 --> 00:12:29.830
neurotransmitter.

00:12:29.830 --> 00:12:32.820
So these are words that you've
probably heard before.

00:12:32.820 --> 00:12:36.070
But anyway, these enter into
the synaptic cleft and then

00:12:36.070 --> 00:12:43.780
they bond on the surface
of the membrane of the

00:12:43.780 --> 00:12:46.100
post-synaptic neuron
or this dendrite.

00:12:49.910 --> 00:12:53.890
Let's say they bond here, they
bond here, and they bond here.

00:12:53.890 --> 00:12:56.560
So they bond on special proteins
on this membrane

00:12:56.560 --> 00:13:02.000
surface, but the main effect of
that is, that will trigger

00:13:02.000 --> 00:13:03.200
ion channels.

00:13:03.200 --> 00:13:07.880
So let's say that this neuron
is exciting this dendrite.

00:13:07.880 --> 00:13:11.540
So when these neurotransmitters
bond on this

00:13:11.540 --> 00:13:14.780
membrane, maybe sodium
channels open up.

00:13:14.780 --> 00:13:18.650
So maybe that will cause a
sodium channel to open up.

00:13:18.650 --> 00:13:20.240
So instead of being voltage
gated, it's

00:13:20.240 --> 00:13:22.050
neurotransmitter gated.

00:13:22.050 --> 00:13:24.950
So this will cause a sodium
channel to open up and then

00:13:24.950 --> 00:13:29.350
sodium will flow in and then,
just like we said before, if

00:13:29.350 --> 00:13:31.970
we go to the original one,
that's like this getting

00:13:31.970 --> 00:13:34.680
excited, it'll become a little
bit positive and then if it's

00:13:34.680 --> 00:13:38.870
enough positive, it'll
electrotonically increase the

00:13:38.870 --> 00:13:41.250
potential at this point on the
axon hillock and then we'll

00:13:41.250 --> 00:13:45.600
have another neuron-- in this
case, this neuron being

00:13:45.600 --> 00:13:46.370
stimulated.

00:13:46.370 --> 00:13:48.070
So that's essentially
how it happens.

00:13:48.070 --> 00:13:49.160
It actually could
be inhibitory.

00:13:49.160 --> 00:13:54.860
You could imagine if this,
instead of triggering a sodium

00:13:54.860 --> 00:14:00.340
ion channel, if it triggered
a potassium ion channel.

00:14:00.340 --> 00:14:04.450
If it triggered a potassium ion
channel, potassium ion's

00:14:04.450 --> 00:14:06.400
concentration gradient will
make it want to go

00:14:06.400 --> 00:14:07.900
outside of the cell.

00:14:07.900 --> 00:14:09.740
So positive things are
going to leave the

00:14:09.740 --> 00:14:11.870
cell if it's potassium.

00:14:11.870 --> 00:14:14.430
Remember, I used triangles
for potassium.

00:14:14.430 --> 00:14:18.430
And so if positive things leave
the cell, then if you go

00:14:18.430 --> 00:14:21.550
further down the neuron, it'll
become less positive and so

00:14:21.550 --> 00:14:25.520
it'll be even harder for the
action potential to start up

00:14:25.520 --> 00:14:29.050
because it'll need even more
positive someplace else to

00:14:29.050 --> 00:14:30.370
make the threshold gradient.

00:14:30.370 --> 00:14:32.300
I hope I'm not confusing
you when I say that.

00:14:32.300 --> 00:14:33.960
So this connection,
the way I first

00:14:33.960 --> 00:14:35.240
described it, it's exciting.

00:14:35.240 --> 00:14:38.140
When this guy gets excited
from an action potential,

00:14:38.140 --> 00:14:39.620
calcium floods in.

00:14:39.620 --> 00:14:43.680
It makes these vesicles dump
their contents in the synaptic

00:14:43.680 --> 00:14:49.680
cleft and then that will make
other sodium gates open up and

00:14:49.680 --> 00:14:51.930
then that will stimulate this
neuron, but if it makes

00:14:51.930 --> 00:14:55.050
potassium gates open up, then
it will inhibit it-- and

00:14:55.050 --> 00:14:59.520
that's how, frankly, these
synapses work.

00:14:59.520 --> 00:15:01.600
I was about to say there's
millions of synapses, but

00:15:01.600 --> 00:15:02.480
that'd be incorrect.

00:15:02.480 --> 00:15:04.840
There's trillions of synapses.

00:15:04.840 --> 00:15:07.870
The best estimate of the number
of synapses in our

00:15:07.870 --> 00:15:18.990
cerebral cortex is 100 to 500
trillion synapses just in the

00:15:18.990 --> 00:15:19.860
cerebral cortex.

00:15:19.860 --> 00:15:22.450
The reason why we can have so
many is that one neuron can

00:15:22.450 --> 00:15:25.840
actually form many, many,
many, many synapses.

00:15:25.840 --> 00:15:27.740
I mean, you can imagine if this
original drawing of a

00:15:27.740 --> 00:15:29.760
cell, you might have a synapse
here, a synapse here, a

00:15:29.760 --> 00:15:30.600
synapse there.

00:15:30.600 --> 00:15:33.680
You could have hundreds or
thousands of synapses even,

00:15:33.680 --> 00:15:36.120
into one neuron or going
out of one neuron.

00:15:36.120 --> 00:15:38.240
This might be a synapse with
one neuron, another one,

00:15:38.240 --> 00:15:39.250
another one, another one.

00:15:39.250 --> 00:15:42.260
So you'd have many, many, many,
many, many connections.

00:15:42.260 --> 00:15:47.220
And so synapses are really what
give us the complexity of

00:15:47.220 --> 00:15:50.400
what probably make us tick in
terms of our human mind and

00:15:50.400 --> 00:15:50.980
all of that.

00:15:50.980 --> 00:15:53.390
But anyway, hopefully you
found this useful.