This FIRST award proposal is to examine the activation of baseline K+ leak channels by volatile anesthetics. Specific aims are (1) to determine the mechanism of channel activation by examining how volatile anesthetics in a range of concentrations alter channel properties, in addition to study the basic physiology and pharmacology of this channel type; (2), to identify and characterize the binding sites at which volatile anesthetics act by examining their ability to occlude actions of endogenous messengers such as arachidonic acid and the ability of halogenated non-anesthetics to act on the channels and to inhibit the actions of isoflurane, and (3) to determine the role of these channels in modulating neuronal excitability and synaptic transmission. Studies will be carried out in cerebellar granule neurons using whole cell ruptured patch and excised patch techniques on neurons in culture and in thin slices.