Rapid stimulation causes electrical remodeling in cultured atrial myocytes.
Rapid stimulation causes electrical remodeling in cultured atrial myocytes.
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DOI：
10.1016/j.yjmcc.2004.11.015
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发表时间：
2005-02-01
影响因子：
5
通讯作者：
Murray, Katherine T
中科院分区：
文献类型：
--
作者：
Yang, Zhenjiang;Shen, Wangzhen;Murray, Katherine T
目的：快速电刺激可引起心房电重构，动作电位时程（APD）缩短，L型钙电流（I（Ca，L））下调，心房颤动（AF）易感性增加。这一过程所需的基本要素目前尚不清楚。我们测试的假设，即快速刺激的心肌细胞在体外是足以概括的重构过程中，心房细胞进行快速起搏的文化将显示类似的变化，发生在vivo.METHODS：心房（HL-1）细胞培养在快速场刺激（300 beats每分钟）的存在下，为24小时。动作电位和离子电流记录从刺激的细胞，以及平行培养的对照细胞，使用全细胞电压钳techniques.RESULTS：快速刺激心房细胞24 h显着缩短APD。HL-1细胞的I（Ca，L）可被尼莫地平阻断，而T型Ca ~（2+）电流（I（Ca，T））则对米贝拉地尔敏感。培养中的快速激活引起I（Ca，L）的下调，而I（Ca，T）也同样减少。多个外向电流是目前在响应去极化电压钳协议，快速起搏导致的快速激活延迟整流K+电流，I（Kr）.CONCLUSIONS：快速刺激培养的心房细胞产生电重构，概括房性心动过速在体内重构的主要表型特征。我们的研究结果表明，这一过程的一个重要组成部分是细胞自主的，因为在体内条件下不需要电重塑的发展。
OBJECTIVE: Rapid stimulation causes electrical remodeling in the intact atrium, with shortening of action potential duration (APD), down-regulation of L-type Ca2+ currents (I(Ca,L)), and increased vulnerability to atrial fibrillation (AF). The essential elements required for this process are currently unknown. We tested the hypothesis that rapid stimulation of cardiomyocytes in vitro is sufficient to recapitulate the remodeling process, and that atrial cells subjected to rapid pacing in culture would display changes similar to those that occur in vivo.METHODS: Atrial (HL-1) cells were cultured in the presence of rapid field stimulation (300 beats per min) for 24 h. Action potentials and ionic currents were recorded from stimulated cells, as well as control cells cultured in parallel, using whole-cell voltage-clamp techniques.RESULTS: Rapid stimulation of atrial cells for 24 h significantly shortened APD. HL-1 cells displayed both I(Ca,L) blocked by nimodipine, and T-type Ca2+ currents (I(Ca,T)) sensitive to mibefradil. Rapid activation in culture caused down-regulation of I(Ca,L), while I(Ca,T) was similarly reduced. Multiple outward currents were present in response to a depolarizing voltage-clamp protocol, and rapid pacing resulted in up-regulation of the rapidly-activating delayed rectifier K+ current, I(Kr).CONCLUSIONS: Rapid stimulation of atrial cells in culture produces electrical remodeling, recapitulating principal phenotypic features of atrial tachycardia remodeling in vivo. Our results demonstrate that an important component of this process is cell autonomous, given that in vivo conditions are not required for the development of electrical remodeling.