Characterization of a [Ca2+]i-dependent current in human atrial and ventricular cardiomyocytes in the absence of Na+ and K+
Characterization of a [Ca2+]i-dependent current in human atrial and ventricular cardiomyocytes in the absence of Na+ and K+
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DOI：
10.1016/s0008-6363(98)00202-8
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发表时间：
1999-01-01
影响因子：
10.8
通讯作者：
Beuckelmann, DJ
中科院分区：
文献类型：
--
作者：
Köster, OF;Szigeti, GP;Beuckelmann, DJ
目的：在[Ca2+](i)-过载的情况下，心律失常被认为是由瞬态内向电流i - tl产生的延迟后去极化触发的。本研究旨在研究在没有Na+/Ca2+交换器的情况下，[Ca2+](i)依赖的膜电流是否可能是人类心脏细胞中i - tl的贡献者。方法：采用全细胞电压钳技术对人心房和心室心肌细胞进行电生理测量。[Ca2+](i)-测量使用荧光Ca2+指示剂fura-2进行。所有溶液都不含Na+。电压无关[Ca2+](i)瞬态引起快速咖啡因应用。结果：心房肌细胞在缺乏Na+和K+的情况下，咖啡因可诱导瞬时膜电流。该电流可被内部EGTA （10 mM）抑制。氯离子对这一洋流没有贡献。实验表明，不同阳离子对Cs+和Li+无选择性，而n-甲基- d -氨基葡萄糖则具有不渗透性。电压斜坡在+80 ~ -80 mV范围内呈线性的电流-电压关系。荧光测量显示电流和体积[Ca2+](i)信号的时间过程之间的解离。在心室心肌细胞中，咖啡因未能在22例不同的晚期心力衰竭患者或非晚期心力衰竭患者的54个细胞中诱导瞬时电流。结论：在人心房心肌细胞中，[Ca2+](i)-依赖性非特异性阳离子通道表达，并可能在[Ca2+](i)-过载的情况下引发心律失常。没有证据表明心房细胞中存在[Ca2+](i)依赖性氯离子电流。在心室细胞中，既不表达[Ca2+](i)依赖性非特异性阳离子通道，也不表达[Ca2+](i)依赖性氯离子通道。因此，人心室心肌可能延迟的去极化后可能仅由Na+/Ca2+交换器携带。(C) 1999 Elsevier Science B.V.版权所有
Objectives: In situations of [Ca2+](i)-overload, arrhythmias are believed to be triggered by delayed afterdepolarizations, which are generated by a transient inward current I-Tl. This study was designed to examine [Ca2+](i)-dependent membrane currents in the absence of the Na+/Ca2+-exchanger as possible contributors to I-Tl in human cardiac cells. Methods: The whole cell voltage clamp technique was used for electrophysiological measurements in human atrial and ventricular cardiomyocytes. [Ca2+](i)-measurements were performed using the fluorescent Ca2+-indicator fura-2. All solutions were Na+-free. Voltage-independent [Ca2+](i)-transients were elicited by rapid caffeine applications. Results: In atrial myocytes, caffeine induced a transient membrane current in the absence of Na+ and K+. This current could be suppressed by internal EGTA (10 mM). Cl- did not contribute to this current. Experiments with different cations suggested non-selectivity for Cs+ and Li+, whereas N-methyl-D-glucamine appeared to be impermeable. Voltage ramps indicated a linear current-voltage relation in the range of +80 to -80 mV. Fluorescence measurements revealed a dissociation between the time courses of current and bulk [Ca2+](i)-signal. In ventricular cardiomyocytes, caffeine failed to induce transient currents in 54 cells from 22 different patients with or without terminal heart failure. Conclusions: In human atrial cardiomyocytes, a [Ca2+](i)-dependent nonspecific cation channel is expressed and may contribute to triggered arrhythmias in situations of [Ca2+](i)-overload. No evidence could be found for the existence of a [Ca2+](i)-dependent chloride current in atrial cells. In ventricular cells, neither a [Ca2+](i)-dependent nonspecific cation channel nor a [Ca2+](i)-dependent chloride channel seems to be expressed. Possible delayed afterdepolarizations in human ventricular myocardium might therefore be carried by the Na+/Ca2+-exchanger alone. (C) 1999 Elsevier Science B.V. All rights reserved.