title: Neuronal activity regulates phosphorylation-dependent surface delivery of G protein-activated inwardly rectifying potassium channels.
abstract: G protein-activated inwardly rectifying K(+) (GIRK) channels regulate neuronal excitability by mediating inhibitory effects of G protein-coupled receptors for neurotransmitters and neuromodulators. Notwithstanding many studies reporting modulation of GIRK channel function, whether neuronal activity regulates GIRK channel trafficking remains an open question. Here we report that NMDA receptor activation in cultured dissociated hippocampal neurons elevates surface expression of the GIRK channel subunits GIRK1 and GIRK2 in the soma, dendrites, and dendritic spines within 15 min. This activity-induced increase in GIRK surface expression requires protein phosphatase-1-mediated dephosphorylation of a serine residue (Ser-9) preceding the GIRK2 Val-13/Leu-14 (VL) internalization motif, thereby promoting channel recycling. Because activation of GIRK channels hyperpolarizes neuronal membranes, the NMDA receptor-induced regulation of GIRK channel trafficking may represent a dynamic adjustment of neuronal excitability in response to inhibitory neurotransmitters and/or neuromodulators.
authors.affiliation: Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Chung
authors.forename: Xiang
authors.initials: X
authors.lastname: Qian
authors.forename: Melissa
authors.initials: M
authors.lastname: Ehlers
authors.forename: Yuh Nung
authors.initials: YN
authors.lastname: Jan
authors.forename: Lily Yeh
authors.initials: LY
authors.lastname: Jan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D008564:Membrane Potentials; D009474:Neurons / Q000502:physiology*; D010766:Phosphorylation; D021381:Protein Transport; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C497070:Kcnj6 protein, rat; D016194:Receptors, N-Methyl-D-Aspartate