Receptor stimulation causes slow inhibition of IRK1 inwardly rectifying K+ channels by direct protein kinase A-mediated phosphorylation
Receptor stimulation causes slow inhibition of IRK1 inwardly rectifying K+ channels by direct protein kinase A-mediated phosphorylation
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DOI：
10.1073/pnas.93.12.5819
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发表时间：
1996-06-11
影响因子：
11.1
通讯作者：
Karschin, A
中科院分区：
文献类型：
--
作者：
Wischmeyer, E;Karschin, A
强整流irk型内整流K+通道参与哺乳动物大脑神经元兴奋性的控制。全细胞膜片钳实验表明，克隆大鼠IRK1 （Kir 2.1）通道在哺乳动物COS-7细胞中异源表达时，受体激动剂激活共表达的5-羟色胺1A型受体后，IRK1 （Kir 2.1）通道被抑制。体内灌注GTP[γ - s]和升高体内cAMP浓度可以模拟抑制作用。将蛋白激酶A （PKA）的催化亚基添加到内部记录溶液中，可以完全抑制野生型IRK1通道，但不会抑制突变型IRK1（S425N）通道，其中c端PKA磷酸化位点已被去除。我们的数据表明，在神经系统中，5 -羟色胺可能通过直接pka介导的磷酸化负性控制IRK1通道活性。
Strongly rectifying IRK-type inwardly rectifying K+ channels are involved in the control of neuronal excitability in the mammalian brain. Whole cell patch-clamp experiments show that cloned rat IRK1 (Kir 2.1) channels, when heterologously expressed in mammalian COS-7 cells, are inhibited following the activation of coexpressed serotonin (5-hydroxytryptamine) type 1A receptors by receptor agonists. Inhibition is mimicked by internal perfusion with GTP[gamma-S] and elevation of internal cAMP concentrations. Addition of the catalytic subunits of protein kinase A (PKA) to the internal recording solution causes complete inhibition of wild-type IRK1 channels, but not of mutant IRK1(S425N) channels in which a C-terminal PKA phosphorylation site has been removed. Our data suggest that in the nervous system serotonin may negatively control IRK1 channel activity by direct PKA-mediated phosphorylation.