Arrhythmogenic consequences of intracellular calcium waves
Arrhythmogenic consequences of intracellular calcium waves
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DOI：
10.1152/ajpheart.00390.2009
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发表时间：
2009-09-01
影响因子：
4.8
通讯作者：
Weiss, James N.
中科院分区：
文献类型：
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作者：
Xie, Lai-Hua;Weiss, James N.
谢金华，魏斯JN.细胞内钙波的致心律失常后果。Am J Physiol心脏圈Physiol 297：H997-H1002,2009。2009年6月26日首次出版；doi：10.1152/ajpheart.00390.2009-细胞内Ca(2+)(Ca(I)(2+))波已知可引起延迟后除极(DADS)，这与心脏病状态下的心律失常有关，如心力衰竭、儿茶酚胺能多形性室性心动过速和洋地黄毒性。这里我们发现，除了DAD，Ca(I)(2+)波还与心律失常的发生有关，包括亚细胞空间不协调交替(SDA)，局部Ca(I)(2+)瞬变的幅度在同一细胞的不同区域异相变化，突然的复极变化促进不应期离散，以及早期后除极(EADS)。在以恒定或递增频率起搏的Fluo-4 AM负载的兔心室肌细胞上，使用电荷耦合装置成像Ca(I)(2+)，使用场刺激、电流钳或动作电位(AP)钳。Ca(I)(2+)波由Bay K 8644(50 NM)+异丙肾上腺素(100 NM)或低温诱导。当起搏开始于自发的Ca(I)(2+)波时，SDA突然出现，并在起搏过程中持续。同样，在快速起搏过程中，SDA通常从空间协调的交替中突然出现，这是由于心肌细胞某一区域的亚细胞内Ca(I)(2+)瞬变的突然相位反转。AP触发的Ca(I)(2+)瞬变可见Ca(I)(2+)波的穿插，产生丰富多样的亚细胞Ca(I)(2+)瞬变模式。在自由运行的AP中，复杂的Ca(I)(2+)释放模式与DADS、EADS和AP持续时间的突变相关。这些发现将Ca(I)(2+)波直接与与完整心脏相关的各种致心律失常现象联系起来。
Xie LH, Weiss JN. Arrhythmogenic consequences of intracellular calcium waves. Am J Physiol Heart Circ Physiol 297: H997-H1002, 2009. First published June 26, 2009; doi: 10.1152/ajpheart.00390.2009.-Intracellular Ca(2+) (Ca(i)(2+)) waves are known to cause delayed afterdepolarizations (DADs), which have been associated with arrhythmias in cardiac disease states such as heart failure, catecholaminergic polymorphic ventricular tachycardia, and digitalis toxicity. Here we show that, in addition to DADs, Ca(i)(2+) waves also have other consequences relevant to arrhythmogenesis, including subcellular spatially discordant alternans (SDA, in which the amplitude of the local Ca(i)(2+) transient alternates out of phase in different regions of the same cell), sudden repolarization changes promoting the dispersion of refractoriness, and early afterdepolarizations (EADs). Ca(i)(2+) was imaged using a charge-coupled device-based system in fluo-4 AM-loaded isolated rabbit ventricular myocytes paced at constant or incrementally increasing rates, using either field stimulation, current clamp, or action potential (AP) clamp. Ca(i)(2+) waves were induced by Bay K 8644 (50 nM) + isoproterenol (100 nM), or low temperature. When pacing was initiated during a spontaneous Ca(i)(2+) wave, SDA occurred abruptly and persisted during pacing. Similarly, during rapid pacing, SDA typically arose suddenly from spatially concordant alternans, due to an abrupt phase reversal of the subcellular Ca(i)(2+) transient in a region of the myocyte. Ca(i)(2+) waves could be visualized interspersed with AP-triggered Ca(i)(2+) transients, producing a rich variety of subcellular Ca(i)(2+) transient patterns. With free-running APs, complex Ca(i)(2+) release patterns were associated with DADs, EADs, and sudden changes in AP duration. These findings link Ca(i)(2+) waves directly to a variety of arrhythmogenic phenomena relevant to the intact heart.