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首页> 外文期刊>American Journal of Physiology >Effect of carvedilol on atrial excitation-contraction coupling, Ca~2+ release, and arrhythmogenicity.
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Effect of carvedilol on atrial excitation-contraction coupling, Ca~2+ release, and arrhythmogenicity.

机译：卡维地洛对心房激发收缩偶联，Ca〜2 +释放和心血发生性的影响。

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摘要

Carvedilol is an FDA-approved beta-blocker commonly used for treatment of high blood pressure, congestive heart failure, and cardiac tachyar-rhythmias, including atrial fibrillation. We investigated at the cellular level the mechanisms through which carvedilol interferes with sarco-plasmic reticulum (SR) Ca~2+ release during excitation-contraction coupling (ECC) in single rabbit atrial myocytes. Carvedilol caused concentration-dependent (1-10 muM) failure of SR Ca~2+ release. Failure of ECC and Ca~2+ release was the result of dose-dependent inhibition of voltage-gated Na~+ (I_Na) and L-type Ca~2+ (I_Ca) currents that are responsible for the rapid depolarization phase of the cardiac action potential (AP) and the initiation of Ca~2+-induced Ca~2+ release from the SR, respectively. Carvedilol (1 p,M) led to AP duration shortening, AP failures, and peak I_Na inhibition by -80%, whereas I_Ca was not markedly affected. Carvedilol (10 muM) blocked I_Na almost completely and reduced I_Ca by approx40%. No effect on Ca~2+-transient amplitude, I_Ca, and I_Na was observed in control experiments with the beta-blocker metoprolol, suggesting that the carvedilol effect on ECC is unlikely the result of its beta-blocking property. The effects of carvedilol (1 muM) on subcellular SR Ca~2+ release was spatially inhomogeneous, where a selective inhibition of peripheral subsarcolemmal Ca~2+ release from the junctional SR accounted for the cell-averaged reduction in Ca~2+-transient amplitude. Furthermore, carvedilol significantly reduced the probability of spontaneous arrhythmogenic Ca~2+ waves without changes of SR Ca~2+ load. The data suggest a profound antiarrhythmic action of carvedilol in atrial myocytes resulting from an inhibitory effect on the SR Ca~2+ release channel.
机译：Carvedilol是一种FDA批准的β-封锁仪，通常用于治疗高血压，充血性心力衰竭和心脏炎动力节律，包括心房颤动。我们在蜂窝水平上调查了Carvedilol在单一兔心房肌细胞中激发 - 收缩偶联（ECC）期间通过该机制通过该机制通过其通过在激发 - 收缩偶联（ECC）中释放的机制。 Carvedilol引起浓度依赖性（1-10毫米）的SR Ca〜2 +释放。 ECC和Ca〜2 +释放的损失是对电压的Na〜+（I_NA）和L型Ca〜2 +（I_CA）电流的剂量依赖性抑制的结果，其负责心脏的快速去极化阶段动作电位（AP）和来自SR的Ca〜2 + -2 +释放的Ca〜2 +释放。 Carvedilol（1 p，m）导致AP持续时间缩短，AP故障和峰值I_NA抑制-80％，而i_CA没有显着影响。 Carvedilol（10毫米）封闭I_NA几乎完全，降低了I_CA大约40％。在对照实验中没有对Ca〜2 + -Transient幅度，I_Ca和I_NA的影响，β-嵌体甲型托洛尔暗示了对ECC对ECC的影响不太可能是其β阻断性的结果。 Carvedilol（1 amum）对亚细胞Sr Ca〜2 +释放的影响是空间不均匀的，其中从结Sr的外周子淋巴瘤Ca〜2释放的选择性抑制占Ca〜2 +--转换的细胞平均降低振幅。此外，卡维地洛显着降低了自发性心律源Ca〜2 +波的概率，而无需SR Ca〜2 +负荷的变化。该数据表明，由于SR Ca〜2 +释放通道的抑制作用，Carvedilol在心房肌细胞中的深刻抗心律失常作用。

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