REGULATION OF ACETYLCHOLINE RECEPTORS ON MUSCLE

State University New York Stony Brook, Stony Brook NY

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Abstract

DESCRIPTION (Adapted from applicant's abstract and specific aims): The long range goal of this research is to gain a better understanding of the mechanisms underlying chemical transmission between nerve and muscle. The studies continue to center on the Xenopus neuromuscular junction which is uniquely amenable to molecular and physiological manipulations. Experiments in past years have focused on identification of the structural features which account for differences in acetylcholine (ACh) receptor properties during synapse development. These studies resulted in the assignment of structural determinants to critical functional properties of the ACh receptor. The specific aims are to: 1) establish the mechanisms underlying each of the two sequential developmental changes in channel open time observed for muscle ACh receptors; 2) determine the roles of high and low affinity ACh binding sites in conferring against sensitivities of different receptor types; 3) further establish a role for cAMP-dependent phosphorylation of ACh receptor subunits in determining desensitization kinetics; and 4) establish the relationships among presynaptic calcium channel kinetics, presynaptic action potential waveform, and the activation of postsynaptic ACh receptors at the neuromuscular junction.