The objective of the proposed research project is to analyze the action of acetylcholine on the K exchange of the sinus node. Acetylcholine increases the K exchange of the sinus node and so does norepinephrine. Since acetylcholine is known to release norepinephrine, K exchange will be investigated by administering acetylcholine before and after depleting the catecholamine store in the sinus node. Since acetylcholine is known to affect intracellular levels of substrates which may interfere with the function of sodium-potassium pump, several agents will be employed to clarify this point. The inhibition and stimulation by acetylcholine is bound to reflect different steps located at different levels. This will require an analysis by appropriate procedures. Finally, the composition of the external environment will be varied to study the requirements for acetylcholine effects. The tissue employed will be the sinus node of the guinea pig which will be initially loaded with 42K. The uptake will be studied by re-exposing the tissue to radioactive Tyrode and measuring the tissue radioactivity at the end of the uptake period. Both spontaneously firing and driven preparations will be used. A microelectrode technique will be employed to record transmembrane potential.