Ablation of a Ca2+-activated K+ channel (SK2 channel) results in action potential prolongation in atrial myocytes and atrial fibrillation
Ablation of a Ca2+-activated K+ channel (SK2 channel) results in action potential prolongation in atrial myocytes and atrial fibrillation
复制标题
Ca2 激活 K 通道（SK2 通道）的消融导致心房肌细胞动作电位延长和心房颤动
DOI：
10.1113/jphysiol.2008.167718
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发表时间：
2009-03-01
影响因子：
5.5
通讯作者：
Chiamvimonvat, Nipavan
中科院分区：
文献类型：
--
作者：
Li, Ning;Timofeyev, Valeriy;Chiamvimonvat, Nipavan
小电导Ca 2+激活的K+通道（SK通道）已在可兴奋细胞中被报道，其中它们有助于将细胞内Ca 2+（Ca 1（2+））的变化与膜电位整合。我们最近报道了SK2通道在人类和小鼠心肌细胞中的功能存在。此外，我们已经发现，该通道主要表达在心房相比，心室肌细胞。我们假设SK2通道的敲除可能足以破坏心房肌细胞复极过程中内向和外向电流的复杂平衡。我们进一步预测，SK2通道的敲除可能使心房易于发生快速性心律失常，因为心脏动作电位的晚期非常容易受到异常兴奋的影响。我们利用SK2通道基因基因敲除的小鼠模型。进行了体内和体外电生理学研究以探测SK2通道在心脏中的功能作用。全细胞膜片钳技术显示了显着延长的动作电位时程显着在晚期心脏复极心房肌细胞从杂合子和纯合子无效突变动物。此外，在体内电生理记录显示诱导心房颤动的空突变小鼠，但不是野生型动物。在无效突变小鼠或野生型动物中未检测到室性心律失常。总之，我们的数据支持SK 2通道在心房肌细胞心脏复极中的重要功能作用。SK2通道的基因敲除导致心脏复极延迟和房性心律失常。
Small conductance Ca2+-activated K+ channels (SK channels) have been reported in excitable cells, where they aid in integrating changes in intracellular Ca2+ (Ca-i(2+)) with membrane potential. We have recently reported the functional existence of SK2 channels in human and mouse cardiac myocytes. Moreover, we have found that the channel is predominantly expressed in atria compared to the ventricular myocytes. We hypothesize that knockout of SK2 channels may be sufficient to disrupt the intricate balance of the inward and outward currents during repolarization in atrial myocytes. We further predict that knockout of SK2 channels may predispose the atria to tachy-arrhythmias due to the fact that the late phase of the cardiac action potential is highly susceptible to aberrant excitation. We take advantage of a mouse model with genetic knockout of the SK2 channel gene. In vivo and in vitro electrophysiological studies were performed to probe the functional roles of SK2 channels in the heart. Whole-cell patch-clamp techniques show a significant prolongation of the action potential duration prominently in late cardiac repolarization in atrial myocytes from the heterozygous and homozygous null mutant animals. Morover, in vivo electrophysiological recordings show inducible atrial fibrillation in the null mutant mice but not wild-type animals. No ventricular arrhythmias are detected in the null mutant mice or wild-type animals. In summary, our data support the important functional roles of SK2 channels in cardiac repolarization in atrial myocytes. Genetic knockout of the SK2 channels results in the delay in cardiac repolarization and atrial arrhythmias.