Unique properties of the ATP-sensitive K⁺ channel in the mouse ventricular cardiac conduction system.
Unique properties of the ATP-sensitive K⁺ channel in the mouse ventricular cardiac conduction system.
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DOI：
10.1161/circep.111.964643
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Coetzee WA
中科院分区：
文献类型：
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作者：
Bao L;Kefaloyianni E;Lader J;Hong M;Morley G;Fishman GI;Sobie EA;Coetzee WA
专门的心脏传导系统（CCS）表达了一种独特的补充离子通道，赋予特定的电生理概况。这些心肌细胞中的ATP敏感性钾（KATP）通道尚未进行系统研究。我们使用Cntn 2-EGFP报告小鼠记录了分离的CCS心肌细胞中的KATP通道。CCS KATP通道对抑制性胞浆ATP的敏感性低于心室通道，并且被MgADP更强烈地激活。他们也有一个较小的斜率电导。这两种通道的爆发内开放和关闭时间相似，但CCS KATP通道的爆发间关闭时间延长。CCS KATP通道被二氮嗪强烈激活，而左克罗卡林激活较少，而心室KATP通道具有相反的药理学特征。CCS心肌细胞表达升高水平的Kir6.1，但减少Kir6.2和SUR 2A mRNA相比，心室肌细胞（SUR 1表达可忽略不计）。CCS心肌细胞中SUR 2B mRNA表达高于SUR 2A。犬浦肯野纤维Kir6.1和SUR 2B蛋白表达水平高于心室。数值模拟预测浦肯野动作电位对ATP：ADP比值变化的高度敏感性。在离体灌流的小鼠心脏中，低流量缺血可延长心脏传导时间，格列本脲可预防这种情况。这些数据意味着在缺血期间心室CCS对KATP通道开放的不同电生理反应（以及可能导致心律失常）。
The specialized cardiac conduction system (CCS) expresses a unique complement of ion channels that confer a specific electrophysiological profile. ATP sensitive potassium (KATP) channels in these myocytes have not been systemically investigated. We recorded KATP channels in isolated CCS myocytes using Cntn2-EGFP reporter mice. The CCS KATP channels were less sensitive to inhibitory cytosolic ATP compared to ventricular channels and more strongly activated by MgADP. They also had a smaller slope conductance. The two types of channels had similar intraburst open and closed times, but the CCS KATP channel had a prolonged interburst closed time. CCS KATP channels were strongly activated by diazoxide and less by levcromakalim, whereas the ventricular KATP channel had a reverse pharmacological profile. CCS myocytes express elevated levels of Kir6.1, but reduced Kir6.2 and SUR2A mRNA compared to ventricular myocytes (SUR1 expression was negligible). SUR2B mRNA expression was higher in CCS myocytes relative to SUR2A. Canine Purkinje fibers expressed higher levels of Kir6.1 and SUR2B protein relative to the ventricle. Numerical simulation predicts a high sensitivity of the Purkinje action potential to changes in ATP:ADP ratio. Cardiac conduction time was prolonged by low-flow ischemia in isolated, perfused mouse hearts, which was prevented by glibenclamide. These data imply a differential electrophysiological response (and possible contribution to arrhythmias) of the ventricular CCS to KATP channel opening during periods of ischemia.