Molecular identification and functional roles of a Ca2+-activated K+ channel in human and mouse hearts
Molecular identification and functional roles of a Ca2+-activated K+ channel in human and mouse hearts
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DOI：
10.1074/jbc.m307508200
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发表时间：
2003-12-05
影响因子：
4.8
通讯作者：
Chiamvimonvat, N
中科院分区：
文献类型：
--
作者：
Xu, YF;Tuteja, D;Chiamvimonvat, N
心脏动作电位的复极期容易出现异常兴奋，这在心脏病患者中很常见。在这里，我们证明了这一时相对钙离子非常敏感，因为在心肌细胞中存在令人惊讶的钙激活的K+电流。电流是使用保存内源性钙缓冲的记录条件来揭示的。Ca~(2+)激活的K~+电流在心房和心室有不同的表达。由于电流对心肌细胞膜复极的重要贡献，电流大小的改变会引起动作电位的异常。我们通过Western印迹分析和逆转录-聚合酶链式反应证实人和小鼠心肌细胞中存在一种小电导钙激活钾通道亚型(SK2)，并克隆了人、小鼠心房和心室的SK2通道。由于SK2通道在心脏中的显著差异表达，钙激活K+电流的特异性配体可能提供一个独特的治疗机会，在不干扰心室肌细胞的情况下修饰心房细胞。
The repolarization phase of cardiac action potential is prone to aberrant excitation that is common in cardiac patients. Here, we demonstrate that this phase is markedly sensitive to Ca2+ because of the surprising existence of a Ca2+-activated K+ currents in cardiac cells. The current was revealed using recording conditions that preserved endogenous Ca2+ buffers. The Ca2+-activated K+ current is expressed differentially in atria compared with ventricles. Because of the significant contribution of the current toward membrane repolarization in cardiac myocytes, alterations of the current magnitude precipitate abnormal action potential profiles. We confirmed the presence of a small conductance Ca2+-activated K+ channel subtype (SK2) in human and mouse cardiac myocytes using Western blot analysis and reverse transcription-polymerase chain reaction and have cloned SK2 channels from human atria, mouse atria, and ventricles. Because of the marked differential expression of SK2 channels in the heart, specific ligands for Ca2+-activated K+ currents may offer a unique therapeutic opportunity to modify atrial cells without interfering with ventricular myocytes.