Regulation of IRK3 inward rectifier K+ channel by m1 acetylcholine receptor and intracellular magnesium.
Inward rectifier K+ channels control the cell's membrane potential and neuronal excitability. We report that the IRK3 but not the IRK1 inward rectifier K+ channel activity is inhibited by m1 muscarinic acetylcholine receptor. This m1 modulation cannot be accounted for by protein kinase C, Ca2+, or channel phosphorylation, but can be mimicked by Mg2+. Based on quantitative analyses of IRK3 and two different IRK1 mutant channels bestowed with sensitivity to m1 modulation, we suggest that the resting Mg2+ level causes chronic inhibition of IRK3 channels, and m1 receptor stimulation may lead to an increase of cytoplasmic Mg2+ concentration and further channel inhibition, due to the ability of Mg2+ to lead these channels into a prolonged inactivated state.
Chuang
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Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco 94143-0724, USA.
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D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004594:Electrophysiology; D005260:Female; D015640:Ion Channel Gating / Q000502:physiology*; D008274:Magnesium / Q000494:pharmacology*; D008322:Mammals; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008969:Molecular Sequence Data; D018721:Muscarinic Agonists / Q000494:pharmacology; D016296:Mutagenesis / Q000502:physiology; D009865:Oocytes / Q000737:chemistry / Q000502:physiology; D010766:Phosphorylation; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism*; D015290:Second Messenger Systems / Q000502:physiology; D012680:Sensitivity and Specificity; D014162:Transfection; D014982:Xenopus laevis
C490969:Kcnj4 protein, mouse; D018721:Muscarinic Agonists; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011976:Receptors, Muscarinic; D008274:Magnesium