Regulation of connexin43 gap junctional conductance by ventricular action potentials
Regulation of connexin43 gap junctional conductance by ventricular action potentials
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DOI：
10.1161/01.res.0000093379.61888.35
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发表时间：
2003-09-19
影响因子：
20.1
通讯作者：
Veenstra, RD
中科院分区：
文献类型：
--
作者：
Lin, XM;Crye, M;Veenstra, RD
跨接电压调节心脏缝隙连接传导，但失活动力学被认为太慢，影响心脏动作电位传播。连接蛋白43（Cx43）在哺乳动物心脏的心房和心室肌以及心室快速传导组织（即His-Purkinje系统）中大量表达，并且对通过这些心脏组织的传导是重要的。使用模拟心室心肌动作电位波形或超过100 mV跨接电位的脉冲协议，在峰值动作电位电压下检查Cx43电压门控的动力学。连接电流响应接近动作电位形态，但电导计算显示从峰值到接近恒定的平台值下降了50%至60%。在第3相复极化和早期恢复至初始值时，连接电导恢复。结电导的这些瞬态变化的基础是在130 mV的峰值跨接电压（V-j）下数十毫秒内的快速衰减动力学以及当V-j向0 mV返回时结电导的逐渐增加。Cx43间隙连接的半失活电压为+/-58 mV，每超过22.1 mV，衰减时间常数变化e倍。一个现实的动态模型，在心脏动作电位传播过程中兴奋和非兴奋细胞之间的连接电阻的变化，开发了基于这些研究结果。这一动态模型的心脏缝隙连接将进一步我们了解的作用，缝隙连接在心律失常的发生和传播。
Transjunctional voltage regulates cardiac gap junctional conductance, but the kinetics of inactivation were considered too slow to affect cardiac action potential propagation. Connexin43 (Cx43) is abundantly expressed in the atrial and ventricular myocardium and the rapid ventricular conduction tissues (ie, His-Purkinje system) of the mammalian heart and is important to conduction through these cardiac tissues. The kinetics of Cx43 voltage gating were examined at peak action potential voltages using simulated ventricular myocardial action potential waveforms or pulse protocols exceeding 100-mV transjunctional potentials. Junctional current responses approximate the action potential morphology but conductance calculations reveal a 50% to 60% decline from peak to near constant plateau values. Junctional conductance recovers during phase 3 repolarization and early diastole to initial values. The bases for these transient changes in junctional conductance are the rapid decay kinetics in tens of milliseconds at peak transjunctional voltages (V-j) of 130 mV and the gradual increase in junctional conductance as V-j returns toward 0 mV. The decay time constants change e-fold per 22.1 mV above the half-inactivation voltage for Cx43 gap junctions of +/-58 mV. A realistic dynamic model for changes in junctional resistance between excitable and nonexcitable cells during cardiac action potential propagation was developed based on these findings. This dynamic model of cardiac gap junctions will further our understanding of the role gap junctions play in the genesis and propagation of cardiac arrhythmias.