Potassium channels of the mammalian presynaptic nerve terminal play a pivotal role in the regulation of synaptic transmission by modulating neuronal excitability. The wide spectrum of physiological properties of these channels, and the inaccessibility to electrophysiological analysis, have combined to limit our understanding of the role of K channels in synaptic transfer and integrated neuronal function. The long term objective is to elucidate the physiological and pharmacological properties of various types of K channels found in presynaptic nerve terminals, so we may eventually come to understand their properties at the molecular level. Preliminary studies of Rb efflux from 86Rb-loaded synaptosomes (pinch-off presynaptic nerve terminals) indicate the presence of several types of K channels in the plasma membranes of the nerve terminals. Therefore, the specific aims of the experiments outlined in this proposal are: 1) To evaluate further the physiological and pharmacological properties of the several classes of K channels observed in this preparation (e.g., Ca-activated; voltage-regulated, inactivating and non-inactivating; and "resting" K conductance). The relative rate of Rb efflux from 86Rb-loaded synaptosomes will be used as a measure of K channel permeability; and 2) To examine the biophysical properties of these conductances by inserting fragments of nerve terminal membranes into planar lipid bilayers in order to study single K channel events. These K channels will be identified by their distinctive pharmacological profiles as revealed by 86Rb efflux experiments. In this way both macroscopic and microscopic properties of identified K channels can be compared, resulting in a more detailed understanding of the types and functions of K channels, from the mamalian central nervous system.