Revisiting the ionic mechanisms of early afterdepolarizations in cardiomyocytes: predominant by Ca waves or Ca currents?
Revisiting the ionic mechanisms of early afterdepolarizations in cardiomyocytes: predominant by Ca waves or Ca currents?
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DOI：
10.1152/ajpheart.00742.2011
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发表时间：
2012-04-01
影响因子：
4.8
通讯作者：
Xie, Lai-Hua
中科院分区：
文献类型：
--
作者：
Zhao, Zhenghang;Wen, Hairuo;Xie, Lai-Hua
赵Z，文H，费费洛娃N，艾伦C，巴巴A，松田T，谢LH.心肌细胞早期后除极离子机制的再探讨：以钙波或钙电流为主？Am J Physiol Heart Circ Physiol 302：H1636-H1644，2012。首次发表于2012年2月3日; doi：10.1152/ajpheart.00742.2011。早期后除极（埃兹）与严重心律失常和心脏性猝死有关。然而，EAD的发生机制，特别是Ca 2+波（CaW）与L型钙电流（I-Ca，I-L）的相对贡献仍存在争议。在本研究中，我们同时记录动作电位（AP）和细胞内钙离子图像在离体兔心室肌细胞和系统地比较埃兹的属性在以下两个药理学模型：1）过氧化氢（H2 O2; 200 μ M）;和2）异丙肾上腺素（100 nM）和BayK 8644（50 nM）（Iso + BayK）。我们评估了埃兹的频率依赖性，埃兹和相应CaW之间的时间关系，埃兹过电压的分布，以及I-Ca，（L），Na/Ca交换剂和ryanodine受体阻断剂的作用。最有说服力的证据来自AP-钳实验，其中细胞膜钳从电流钳切换到电压钳使用正常AP波形没有EAD; CaWs在H2 O2模型中消失，但在Iso + BayK模型中持续存在。我们推测，尽管CaW和I-Ca_i（L）的再激活可能在任一情况下协同作用，但I-Ca_i（L）的再激活在氧化应激下的EAD发生中起主导作用（H_2O_2模型），而自发CaW是Ca ~（2+）过载条件下埃兹的主要原因（Iso + BayK模型）。
Zhao Z, Wen H, Fefelova N, Allen C, Baba A, Matsuda T, Xie LH. Revisiting the ionic mechanisms of early afterdepolarizations in cardiomyocytes: predominant by Ca waves or Ca currents? Am J Physiol Heart Circ Physiol 302: H1636-H1644, 2012. First published February 3, 2012; doi: 10.1152/ajpheart.00742.2011.-Early afterdepolarizations (EADs) have been implicated in severe cardiac arrhythmias and sudden cardiac deaths. However, the mechanism(s) for EAD genesis, especially regarding the relative contribution of Ca2+ wave (CaW) vs. L-type Ca current (I-Ca,I-L), still remains controversial. In the present study, we simultaneously recorded action potentials (APs) and intracellular Ca2+ images in isolated rabbit ventricular myocytes and systematically compared the properties of EADs in the following two pharmacological models: 1) hydrogen peroxide (H2O2; 200 mu M); and 2) isoproterenol (100 nM) and BayK 8644 (50 nM) (Iso + BayK). We assessed the rate dependency of EADs, the temporal relationship between EADs and corresponding CaWs, the distribution of EADs over voltage, and the effects of blockers of I-Ca,(L), Na/Ca exchangers, and ryanodine receptors. The most convincing evidence came from the AP-clamp experiment, in which the cell membrane clamp was switched from current clamp to voltage clamp using a normal AP waveform without EAD; CaWs disappeared in the H2O2 model, but persisted in the Iso + BayK model. We postulate that, although CaWs and reactivation of I-Ca,(L) may act synergistically in either case, reactivation of I-Ca,(L) plays a predominant role in EAD genesis under oxidative stress (H2O2 model), while spontaneous CaWs are a predominant cause for EADs under Ca2+ overload condition (Iso + BayK model).