Gasotransmitters and Plasticity at teh Excitatory Synapse

Johns Hopkins University, Baltimore MD

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Abstract

Glutamate-AMPA receptors are the key mediators of excitatory transmission of which GluA1 is a major subtype. GluA1's conductance is critically determined by phosphorylation at serine-831. We recently discovered that nitric oxide (NO) nitrosylates GluA1 at a specific cysteine, C875. and that this nitrosylation determines S831 phosphorylation. We plan to elucidate mechanisms underlying this important mode of regulation. We will also explore the impact of hydrogen sulfide (H2S) modifying, via sulfhydration, C875 in presumed reciprocity with nitrosylation. We earlier showed that nitrosylation of stargazin, a major auxiliary protein of AMPA receptors, determines GluA1 conductance. We will explore regulation of this process and how it interfaces with gasotransmitter influences exerted directly upon GluA1.