Pacing-induced heterogeneities in intracellular Ca2+ signaling, cardiac alternans, and ventricular arrhythmias in intact rat heart
Pacing-induced heterogeneities in intracellular Ca2+ signaling, cardiac alternans, and ventricular arrhythmias in intact rat heart
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DOI：
10.1161/01.res.0000244087.36230.bf
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发表时间：
2006-09-29
影响因子：
20.1
通讯作者：
Wasserstrom, J. Andrew
中科院分区：
文献类型：
--
作者：
Aistrup, Gary L.;Kelly, James E.;Wasserstrom, J. Andrew
光学作图研究表明，细胞内Ca2+和t波交替是通过Ca2+敏感电导在动作电位持续时间内的Ca2+循环诱导振荡的潜在变化联系在一起的。然而，这些研究不能测量单细胞行为；因此，微观心室区域内Ca2+循环的异质性是未知的。本研究的目的是测量快速起搏和心律失常期间完整心肌的细胞活性。我们使用单光子激光扫描共聚焦显微镜测量了在快速起搏和起搏引起的室性心律失常期间，完整大鼠心肌单个肌细胞中的Ca2+信号。在低速率下，所有肌细胞都表现出同步的Ca2+交替，但其大小取决于每个肌细胞Ca2+循环的恢复动力学。随着速率的增加，一些细胞逆转交替期，产生不同步的激活模式，甚至在相邻的肌细胞中也是如此。增加的起搏速率也诱导亚细胞交替，其中Ca2+在同一细胞内的不同区域发生异相交替。这些形式的异质Ca2+信号也发生在起搏诱导的室性心动过速。我们的研究结果表明，在快速起搏和心律失常期间，完整心脏中单个肌细胞之间和内部的Ca2+信号高度不均匀。因此，某些改变Ca2+循环动力学的病理生理条件，如心力衰竭，可能通过夸大Ca2+信号的细胞异质性来促进室性心律失常。
Optical mapping studies have suggested that intracellular Ca2+ and T-wave alternans are linked through underlying alternations in Ca2+ cycling-inducing oscillations in action potential duration through Ca2+-sensitive conductances. However, these studies cannot measure single-cell behavior; therefore, the Ca2+ cycling heterogeneities within microscopic ventricular regions are unknown. The goal of this study was to measure cellular activity in intact myocardium during rapid pacing and arrhythmias. We used single-photon laser-scanning confocal microscopy to measure Ca2+ signaling in individual myocytes of intact rat myocardium during rapid pacing and during pacing-induced ventricular arrhythmias. At low rates, all myocytes demonstrate Ca2+ alternans that is synchronized but whose magnitude varies depending on recovery kinetics of Ca2+ cycling for each individual myocyte. As rate increases, some cells reverse alternans phase, giving a dyssynchronous activation pattern, even in adjoining myocytes. Increased pacing rate also induces subcellular alternans where Ca2+ alternates out of phase with different regions within the same cell. These forms of heterogeneous Ca2+ signaling also occurred during pacing-induced ventricular tachycardia. Our results demonstrate highly nonuniform Ca2+ signaling among and within individual myocytes in intact heart during rapid pacing and arrhythmias. Thus, certain pathophysiological conditions that alter Ca2+ cycling kinetics, such as heart failure, might promote ventricular arrhythmias by exaggerating these cellular heterogeneities in Ca2+ signaling.