在无钠和钾的情况下对人心房和心室心肌细胞中一种钙离子浓度依赖性电流的特性分析。

Characterization of a [Ca2+]i-dependent current in human atrial and ventricular cardiomyocytes in the absence of Na+ and K+.

作者信息

Köster O F, Szigeti G P, Beuckelmann D J

机构信息

Department of Internal Medicine III, University of Cologne, Germany.

出版信息

Cardiovasc Res. 1999 Jan;41(1):175-87. doi: 10.1016/s0008-6363(98)00202-8.

DOI:10.1016/s0008-6363(98)00202-8

PMID:10325965

Abstract

OBJECTIVES

In situations of [Ca2+]i-overload, arrhythmias are believed to be triggered by delayed afterdepolarizations, which are generated by a transient inward current ITI. This study was designed to examine [Ca2+]i-dependent membrane currents in the absence of the Na+/Ca(2+)-exchanger as possible contributors to ITI 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 Ca(2+)-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+/Ca(2+)-exchanger alone.

摘要

目的

在细胞内钙离子超载的情况下，心律失常被认为是由延迟后除极触发的，而延迟后除极是由瞬时内向电流ITI产生的。本研究旨在检测在没有钠/钙交换体的情况下，人心脏细胞中依赖于细胞内钙离子的膜电流，这些电流可能是ITI的促成因素。

方法

采用全细胞膜片钳技术对人心房和心室心肌细胞进行电生理测量。使用荧光钙指示剂fura-2进行细胞内钙离子测量。所有溶液均无钠。通过快速应用咖啡因诱发与电压无关的细胞内钙离子瞬变。

结果

在心房肌细胞中，咖啡因在无钠和钾的情况下诱发了瞬时膜电流。该电流可被细胞内EGTA（10 mM）抑制。氯离子对该电流无贡献。用不同阳离子进行的实验表明，该电流对铯离子和锂离子无选择性，而N-甲基-D-葡萄糖胺似乎不可通透。电压斜坡显示在+80至-80 mV范围内电流-电压呈线性关系。荧光测量显示电流和整体细胞内钙离子信号的时间进程之间存在解离。在心室心肌细胞中，来自22例不同的有或无终末期心力衰竭患者的54个细胞中，咖啡因未能诱发瞬时电流。

结论

在人心房心肌细胞中，表达了一种依赖于细胞内钙离子的非特异性阳离子通道，在细胞内钙离子超载的情况下可能促成触发心律失常。未发现心房细胞中存在依赖于细胞内钙离子的氯电流的证据。在心室细胞中，似乎既不表达依赖于细胞内钙离子的非特异性阳离子通道，也不表达依赖于细胞内钙离子的氯通道。因此，人心室心肌中可能的延迟后除极可能仅由钠/钙交换体介导。