Department of Medicine (Cardiology), David Geffen School of Medicine at University of California, Los Angeles, CA 90095, USA.
Heart Rhythm. 2013 Apr;10(4):575-82. doi: 10.1016/j.hrthm.2012.12.017. Epub 2012 Dec 12.
Under conditions promoting early afterdepolarizations (EADs), ventricular tissue can become bi-excitable, that is, capable of wave propagation mediated by either the Na current (INa) or the L-type calcium current (ICa,L), raising the possibility that ICa,L-mediated reentry may contribute to polymorphic ventricular tachycardia (PVT) and torsades de pointes. ATP-sensitive K current (IKATP) activation suppresses EADs, but the effects on ICa,L-mediated reentry are unknown.
To investigate the effects of IKATP activation on ICa,L-mediated reentry.
We performed optical voltage mapping in cultured neonatal rat ventricular myocyte monolayers exposed to BayK8644 and isoproterenol. The effects of pharmacologically activating IKATP with pinacidil were analyzed.
In 13 monolayers with anatomic ICa,L-mediated reentry around a central obstacle, pinacidil (50 μM) converted ICa,L-mediated reentry to INa-mediated reentry. In 33 monolayers with functional ICa,L-mediated reentry (spiral waves), pinacidil terminated reentry in 17, converted reentry into more complex INa-mediated reentry resembling fibrillation in 12, and had no effect in 4. In simulated 2-dimensional bi-excitable tissue in which ICa,L- and INa-mediated wave fronts coexisted, slow IKATP activation (over minutes) reliably terminated rotors but rapid IKATP activation (over seconds) often converted ICa,L-mediated reentry to INa-mediated reentry resembling fibrillation.
IKATP activation can have proarrhythmic effects on EAD-mediated arrhythmias if ICa,L-mediated reentry is present.
在促进早期后除极 (EAD) 的条件下，心室组织可能变得双兴奋性，即能够通过钠电流 (INa) 或 L 型钙电流 (ICa,L) 介导的波传播，这增加了 ICa,L 介导的折返可能导致多形性室性心动过速 (PVT) 和尖端扭转型室性心动过速的可能性。ATP 敏感性钾电流 (IKATP) 的激活抑制 EAD，但对 ICa,L 介导的折返的影响尚不清楚。
研究 IKATP 激活对 ICa,L 介导的折返的影响。
我们在暴露于 BayK8644 和异丙肾上腺素的培养的新生大鼠心室肌细胞单层中进行光学电压映射。分析用匹那地尔药理学激活 IKATP 的效果。
在 13 个具有中央障碍物周围解剖学 ICa,L 介导折返的单层中，匹那地尔 (50 μM) 将 ICa,L 介导的折返转换为 INa 介导的折返。在 33 个具有功能性 ICa,L 介导折返 (螺旋波) 的单层中，匹那地尔终止折返 17 次，将折返转换为更复杂的类似于纤维颤动的 INa 介导折返 12 次，而在 4 次无影响。在模拟的 2 维双兴奋性组织中，ICa,L 和 INa 介导的波阵面共存，缓慢的 IKATP 激活 (数分钟) 可靠地终止转子，但快速的 IKATP 激活 (数秒) 经常将 ICa,L 介导的折返转换为类似于纤维颤动的 INa 介导的折返。
如果存在 ICa,L 介导的折返，IKATP 的激活可能对 EAD 介导的心律失常产生致心律失常作用。
