The ICl,swell inhibitor DCPIB blocks Kir channels that possess weak affinity for PIP2.
The ICl,swell inhibitor DCPIB blocks Kir channels that possess weak affinity for PIP2.
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DOI：
10.1007/s00424-016-1794-9
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发表时间：
2016-05
期刊：
影响因子：
--
通讯作者：
Logothetis DE
中科院分区：
文献类型：
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作者：
Deng W;Mahajan R;Baumgarten CM;Logothetis DE
向内整流K+（Kir）通道是静息膜电位的重要贡献者并调节细胞兴奋性。Kir通道的活性主要取决于磷脂PIP2。Kir通道活性的几种调节剂改变通道对PIP2的表观亲和力。对PIP2具有高表观亲和力的通道可能不响应给定的调节剂，但是降低这种亲和力的突变可以使通道对调节敏感。在这里，我们确定了一种已知的肿胀激活Cl−电流抑制剂DCPIB，作为天然心脏细胞和异源表达系统中许多Kir通道的有效抑制剂。我们表明，表观亲和力PIP2决定是否DCPIB将作为一个有效的阻断剂Kir通道。这些效应与DCPIB与PIP2竞争共同结合位点的模型一致。
Inwardly rectifying K+ (Kir) channels are important contributors to the resting membrane potential and regulate cellular excitability. The activity of Kir channels depends critically on the phospholipid PIP2. Several modulators of the activity of Kir channels alter the apparent affinity of the channel to PIP2. Channels with high apparent affinity to PIP2 may not respond to a given modulator, but mutations that decrease such affinity can render the channel susceptible to modulation. Here, we identify a known inhibitor of the swelling-activated Cl− current, DCPIB, as an effective inhibitor of a number of Kir channels both in native cardiac cells and in heterologous expression systems. We show that the apparent affinity to PIP2 determines whether DCPIB will serve as an efficient blocker of Kir channels. These effects are consistent with a model in which DCPIB competes with PIP2 for a common binding site.