Activity-dependent regulation of neuronal GIRK channels

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DESCRIPTION (provided by applicant): G-protein coupled inwardly rectifying potassium channel (GIRK) regulates neuronal excitability by mediating postsynaptic inhibitory effects of various transmitter in brain. Recent studies showing the presence of GIRK in dendritic spines suggest that excitatory neurotransmitter receptors may regulate GIRK function. Indeed, neuronal activity increased GIRK surface expression in dendrites and spines of hippocampal neurons in a protein synthesis and a protein phosphatase (PPI)-dependent manner. The objectives of this proposal are to investigate the molecular mechanisms and physiological consequence of activity-induced GIRK surface expression. Live-imaging and surface immunostaining will be performed to investigate how protein synthesis, post translational surface trafficking of GIRK and PP1 activity contribute to activity-induced GIRK surface expression (Specific Aim A-C). To study the functional significance of activity-induced GIRK surface expression (Specific Aim D), whole-cell patch clamp recording of GABAb-mediated GIRK current before and after neuronal activity will be performed. These studies will reveal novel mechanisms for modulating inhibitory synaptic function