蛋白激酶A刺激心脏钾通道的分子基础。
Molecular basis of cardiac potassium channel stimulation by protein kinase A.
作者信息
Huang X Y, Morielli A D, Peralta E G
机构信息
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.
出版信息
Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):624-8. doi: 10.1073/pnas.91.2.624.
Abstract
Cardiac beta-adrenergic receptors accelerate heart rate by modulating ionic currents through a pathway involving cyclic AMP-dependent protein kinase A (PKA). Previous studies have focused on the regulation of Ca2+ channels by PKA; however, due to the heterogeneity of K+ channels expressed within the heart, little is known about the mechanism by which PKA modulates individual K+ channels. Here we report that PKA strongly enhanced the activity of a cloned delayed rectifier K+ channel that is normally expressed in cardiac atria. This effect required a single PKA consensus phosphorylation site located near the amino terminus of the channel protein. Furthermore, patch clamp analysis revealed that PKA phosphorylation increased the open time that single channels spend in higher conductance states. These studies provide evidence that hormonal modulation of a cardiac K+ channel involves direct phosphorylation by PKA.
摘要
心脏β-肾上腺素能受体通过涉及环磷酸腺苷依赖性蛋白激酶A（PKA）的途径调节离子电流，从而加速心率。以往的研究主要集中在PKA对钙通道的调节；然而，由于心脏中表达的钾通道具有异质性，关于PKA调节单个钾通道的机制知之甚少。在此我们报告，PKA强烈增强了一种克隆的延迟整流钾通道的活性，该通道通常在心脏心房中表达。这种效应需要位于通道蛋白氨基末端附近的单个PKA共有磷酸化位点。此外，膜片钳分析显示，PKA磷酸化增加了单个通道处于更高电导状态的开放时间。这些研究提供了证据，表明心脏钾通道的激素调节涉及PKA的直接磷酸化。
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