Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Cells, Cultured
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Electrophysiology
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Female
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Ion Channel Gating / physiology*
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Magnesium / pharmacology*
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Mammals
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Molecular Sequence Data
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Muscarinic Agonists / pharmacology
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Mutagenesis / physiology
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Oocytes / chemistry
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Oocytes / physiology
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Phosphorylation
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Potassium Channel Blockers*
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Potassium Channels / genetics
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Potassium Channels / metabolism*
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Potassium Channels, Inwardly Rectifying
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Receptors, Muscarinic / genetics
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Receptors, Muscarinic / metabolism*
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Second Messenger Systems / physiology
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Sensitivity and Specificity
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Transfection
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Xenopus laevis
Substances
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Kcnj4 protein, mouse
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Muscarinic Agonists
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Potassium Channel Blockers
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Potassium Channels
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Potassium Channels, Inwardly Rectifying
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Receptors, Muscarinic
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Magnesium