Coordinated signal integration at the M-type potassium channel upon muscarinic stimulation

被引：64

作者：

Kosenko, Anastasia ^{[1
]}

Kang, Seungwoo ^{[1
]}

Smith, Ida M. ^{[1
]}

Greene, Derek L. ^{[1
]}

Langeberg, Lorene K. ^{[2
]}

Scott, John D. ^{[2
]}

Hoshi, Naoto ^{[1
]}

机构：

[1] Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92697 USA

[2] Univ Washington, Dept Pharmacol, Howard Hughes Med Inst, Seattle, WA 98195 USA

来源：

EMBO JOURNAL | 2012年 / 31卷 / 14期

关键词：

calmodulin; protein complex; protein kinase C; signal transduction; voltage-gated potassium channel; HIPPOCAMPAL PYRAMIDAL NEURONS; RECEPTOR-MEDIATED INHIBITION; K+ CHANNELS; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; PLASMA-MEMBRANE; KCNQ CHANNELS; KINASE-C; PIP2; SUPPRESSION; MODULATION;

D O I：

10.1038/emboj.2012.156

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Several neurotransmitters, including acetylcholine, regulate neuronal tone by suppressing a non-inactivating low-threshold voltage-gated potassium current generated by the M-channel. Agonist dependent control of the M-channel is mediated by calmodulin, activation of anchored protein kinase C (PKC), and depletion of the phospholipid messenger phosphatidylinositol 4,5-bisphosphate (PIP2). In this report, we show how this trio of second messenger responsive events acts synergistically and in a stepwise manner to suppress activity of the M-current. PKC phosphorylation of the KCNQ2 channel subunit induces dissociation of calmodulin from the M-channel complex. The calmodulin-deficient channel has a reduced affinity towards PIP2. This pathway enhances the effect of concomitant reduction of PIP2, which leads to disruption of the M-channel function. These findings clarify how a common lipid cofactor, such as PIP2, can selectively regulate ion channels. The EMBO Journal (2012) 31, 3147-3156. doi:10.1038/emboj.2012.156; Published online 29 May 2012

引用

页码：3147 / 3156

页数：10

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