Action potential modulation of connexin40 gap junctional conductance
Action potential modulation of connexin40 gap junctional conductance
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DOI：
10.1152/ajpheart.00943.2003
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发表时间：
2004-05-01
影响因子：
4.8
通讯作者：
Veenstra, RD
中科院分区：
文献类型：
--
作者：
Lin, XM;Veenstra, RD
连接蛋白40（Cx40）在哺乳动物心血管系统的心房肌、心室传导系统、血管内皮细胞和平滑肌细胞中大量表达。通过心脏组织的快速传导依赖于相邻细胞之间动作电位的电紧张性转移。为了确定由动作电位引起的跨接电压（V-j）是否可以调节Cx40间隙连接的电导，将模拟的心肌动作电位作为电压钳波形施加到在小鼠neuro 2A（N2 A）细胞中表达的Cx40间隙连接。连接电流类似于动作电位形态，但从峰值下降>50%至接近恒定的平台值。在峰值电压大于或等于100 mV时检查Cx40电压门控动力学，对于V-j > +/- 40 mV，衰减时间常数每17.6 mV变化e倍。在第3相复极和舒张早期，交界处电导恢复至初始值。结电导的这些阶段性变化是由于快速衰减动力学，在峰值V-j为130 mV时增加到数十毫秒，以及当V-j向0 mV返回时稳态电导曲线的增加。Cx40的时间依赖性电导曲线用一个失活和两个恢复V-j依赖性组分建模。传导延迟或阻滞的发展与交界区传导的失活期之间存在时间相关性。同样，连接电导的恢复与不应期的恢复一致，表明缝隙连接可能在心律失常的发生和传播中发挥作用。
Connexin40 (Cx40) is abundantly expressed in the atrial myocardium, ventricular conduction system, and vascular endothelial and smooth muscle cells of the mammalian cardiovascular system. Rapid conduction through cardiac tissues depends on electrotonic transfer of the action potential between neighboring cells. To determine whether transjunctional voltages (V-j) elicited by an action potential can modulate conductance of Cx40 gap junctions, simulated myocardial action potentials were applied as voltage-clamp waveforms to Cx40 gap junctions expressed in mouse neuro2A (N2A) cells. Junctional currents resembled the action potential morphology but declined by >50% from peak to near-constant plateau values. Kinetics of Cx40 voltage gating were examined at peak voltages greater than or equal to100 mV, and decay time constants changed e-fold per 17.6 mV for V-j > +/- 40 mV. Junctional conductance recovered during phase 3 repolarization and early diastole to initial values. These phasic changes in junctional conductance were due to rapid decay kinetics, increasing to tens of milliseconds at peak V-j of 130 mV, and the increase in the steady-state conductance curve as V-j returned toward 0 mV. Time-dependent conductance curves for Cx40 were modeled with one inactivation and two recovery V-j-dependent components. There was a temporal correlation between development of conduction delay or block and the inactivation phase of junctional conductance. Likewise, recovery of junctional conductance was coincident with recovery from refractoriness, suggesting that gap junctions may play a role in the genesis and propagation of cardiac arrhythmias.