PIP2 and PIP as determinants for ATP inhibition of KATP channels
PIP2 and PIP as determinants for ATP inhibition of KATP channels
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DOI：
10.1126/science.282.5391.1141
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发表时间：
1998-11-06
期刊：
影响因子：
56.9
通讯作者：
Fakler, B
中科院分区：
文献类型：
--
作者：
Baukrowitz, T;Schulte, U;Fakler, B
三磷酸腺苷（ATP）敏感性钾（K-ATP）通道通过其被细胞内ATP抑制而将电活动与细胞代谢偶联。ATP对K-ATP通道的抑制作用在不同组织中存在差异，并受单个细胞代谢和调节状态的影响，这表明内源性因素的参与。本文报道了磷脂酰肌醇-4，5-二磷酸（PIP 2）和磷脂酰肌醇-4-磷酸（PIP）控制克隆的K-ATP通道（K（ir）6.2和SUR 1）的ATP抑制。这些磷脂作用于K（ir）6.2亚基，使ATP敏感性发生几个数量级的变化。受体介导的磷脂酶C激活导致抑制K-ATP介导的电流。这些结果代表了通过磷脂控制兴奋性的机制。
Adenosine triphosphate (ATP)-sensitive potassium (K-ATP) channels couple electrical activity to Cellular metabolism through their inhibition by intracellular ATP. ATP inhibition of K-ATP channels varies among tissues and is affected by the metabolic and regulatory state of individual cells, suggesting involvement of endogenous factors. It is reported here that phosphatidylinositol-4,5-bisphosphate (PIP2) and phosphatidylinositol-4-phosphate (PIP) controlled ATP inhibition of cloned K-ATP channels (K(ir)6.2 and SUR1). These phospholipids acted on the K(ir)6.2 subunit and shifted ATP sensitivity by several orders of magnitude. Receptor-mediated activation of phospholipase C resulted in inhibition of K-ATP-mediated currents. These results represent a mechanism for control of excitability through phospholipids.