Endothelin-A receptor mediates cardiac inhibition by regulating calcium and potassium currents
Endothelin-A receptor mediates cardiac inhibition by regulating calcium and potassium currents
复制标题
内皮素 A 受体通过调节钙和钾电流介导心脏抑制
作者：
K. Ono;G. Tsujimoto;A. Sakamoto;K. Eto;T. Masaki;Y. Ozaki;M. Satake
电压敏感离子通道在多种神经递质对心功能的调节中起着重要作用1,2。内皮素具有强烈的正性肌力和变时作用，最近的研究已经涉及到多种细胞内机制。然而，对这种肽潜在的离子通道调节知之甚少。我们在这里报道，内皮素-1在哺乳动物心房肌细胞中持续地使膜超极化并缩短动作电位的持续时间，导致心脏电兴奋性的抑制。内皮素-1（而非内皮素-3）通过减少环AMP积累抑制l型钙电流，通过刺激百日破毒素敏感的gtp结合蛋白激活毒蕈碱钾电流。与这些结果一致的是，内皮素-1在β-肾上腺素受体刺激下显著降低心率。这些作用被ETA（内皮素-1选择性）受体选择性拮抗剂BQ123阻断（参考文献8-11）。ETA受体介导的心脏离子通道调节为我们对内皮素在心脏功能控制中的生理和病理生理作用的理解提供了新的见解。
VOLTAGE-SENSITIVE ion channels play fundamental roles in the regulation of cardiac function by various neurotransmitters1,2. Endothelins3 have strong positive inotropic4 and chronotropic5 effects, for which recent studies have implicated various intracellular mechanisms6,7. However, very little is known about the underlying ion-channel regulation by the peptide. We report here that endothelin-1 consistently hyperpolarizes the membrane and shortens the duration of the action potential in mammalian atrial myocytes, leading to suppression of electrical excitability of the heart. Endothelin-1, but not endothelin-3, inhibited the L-type calcium current by decreasing cyclic AMP accumulation and activated the muscarinic potassium current by stimulating a pertussis toxin-sensitive GTP-binding protein. Consistent with these results, endothelin-1 strongly reduced the heart rate when it was increased by β-adrenoceptor stimulation. These effects were blocked by an ETA (endothelin-1-selective) receptor-selective antagonist, BQ123 (refs 8–11). The ETA receptor-mediated regulation of cardiac ion channels gives new insight into our understanding of the physiological and pathophysiological roles of endothelins in the control of cardiac function.
内皮素激活心房细胞内向整流 K 电流。
影响因子：
20.1
作者：
Kim,D
通讯作者：
Kim,D
内皮素抑制腺苷酸环化酶并刺激成人心肌细胞中的磷酸肌醇水解。
DOI：
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发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Hilal-Dandan,R;Urasawa,K;Brunton,LL
通讯作者：
Brunton,LL