M1型乙酰胆碱受体和细胞内镁对IRK3内向整流钾通道的调节

Regulation of IRK3 inward rectifier K+ channel by m1 acetylcholine receptor and intracellular magnesium.

作者信息

Chuang H, Jan Y N, Jan L Y

机构信息

Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco 94143-0724, USA.

出版信息

Cell. 1997 Jun 27;89(7):1121-32. doi: 10.1016/s0092-8674(00)80299-8.

DOI:10.1016/s0092-8674(00)80299-8

PMID:9215634

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.

摘要

内向整流钾通道控制细胞膜电位和神经元兴奋性。我们报告称，m1毒蕈碱型乙酰胆碱受体可抑制IRK3内向整流钾通道的活性，而不影响IRK1的活性。这种m1调节作用不能用蛋白激酶C、钙离子或通道磷酸化来解释，但可被镁离子模拟。基于对赋予m1调节敏感性的IRK3和两种不同IRK1突变通道的定量分析，我们认为静息镁离子水平会导致IRK3通道的慢性抑制，而m1受体刺激可能会导致细胞质镁离子浓度升高，进而进一步抑制通道，这是因为镁离子能够使这些通道进入长时间失活状态。