Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Heart Rhythm. 2020 Sep;17(9):1582-1590. doi: 10.1016/j.hrthm.2020.04.023. Epub 2020 Apr 22.
Small-conductance Ca-activated potassium (SK) channels play complex roles in cardiac arrhythmogenesis. SK channels colocalize with L-type Ca channels, yet how this colocalization affects cardiac arrhythmogenesis is unknown.
The purpose of this study was to investigate the role of colocalization of SK channels with L-type Ca channels in promoting J-wave syndrome and ventricular arrhythmias.
We carried out computer simulations of single-cell and tissue models. SK channels in the model were assigned to preferentially sense Ca in the bulk cytosol, subsarcolemmal space, or junctional cleft.
When SK channels sense Ca in the bulk cytosol, the SK current (I) rises and decays slowly during an action potential, the action potential duration (APD) decreases as the maximum conductance increases, no complex APD dynamics and phase 2 reentry can be induced by I. When SK channels sense Ca in the subsarcolemmal space or junctional cleft, I can rise and decay rapidly during an action potential in a spike-like pattern because of spiky Ca transients in these compartments, which can cause spike-and-dome action potential morphology, APD alternans, J-wave elevation, and phase 2 reentry. Our results can account for the experimental finding that activation of I induced J-wave syndrome and phase 2 reentry in rabbit hearts.
Colocalization of SK channels with L-type Ca channels so that they preferentially sense Ca in the subsarcolemmal or junctional space may result in a spiky I, which can functionally play a similar role of the transient outward K current in promoting J-wave syndrome and ventricular arrhythmias.
小电导钙激活钾（SK）通道在心脏心律失常的发生中发挥着复杂的作用。SK 通道与 L 型钙通道共定位，但这种共定位如何影响心脏心律失常的发生尚不清楚。
本研究旨在探讨 SK 通道与 L 型钙通道共定位在促进 J 波综合征和室性心律失常中的作用。
我们进行了单细胞和组织模型的计算机模拟。模型中的 SK 通道被分配为优先感知细胞质、亚细胞间隙或连接间隙中的 Ca。
当 SK 通道感知细胞质中的 Ca 时，在动作电位期间，SK 电流（I）缓慢上升和下降，动作电位持续时间（APD）随着最大电导的增加而减小，I 不能引起复杂的 APD 动力学和 2 相折返。当 SK 通道感知亚细胞间隙或连接间隙中的 Ca 时，由于这些隔室中的 Ca 瞬间尖峰，I 可以在动作电位期间以尖峰样的模式快速上升和下降，这可能导致尖峰-穹顶动作电位形态、APD 交替、J 波抬高和 2 相折返。我们的结果可以解释实验发现，I 的激活在兔心中诱导 J 波综合征和 2 相折返。
SK 通道与 L 型钙通道共定位，使它们优先感知亚细胞间隙或连接间隙中的 Ca，可能导致尖峰样的 I，其在促进 J 波综合征和室性心律失常方面可以发挥类似于瞬时外向钾电流的功能作用。
