Short- and long-term inhibition of cardiac inward-rectifier potassium channel current by an antiarrhythmic drug bepridil
Short- and long-term inhibition of cardiac inward-rectifier potassium channel current by an antiarrhythmic drug bepridil
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DOI：
10.1007/s00380-015-0762-1
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发表时间：
2016-07-01
影响因子：
1.5
通讯作者：
Ono, Katsushige
中科院分区：
文献类型：
--
作者：
Ma, Fangfang;Takanari, Hiroki;Ono, Katsushige
贝普利地尔是一种有效的抗室上性和室性心律失常药物，也是钙调素抑制剂。最近的研究表明，贝普利地尔通过急性和慢性应用于患者发挥抗心律失常的作用。本研究的目的是确定贝必地尔在急性和长期条件下对新生大鼠心肌细胞内整流钾通道的疗效及其潜在机制。Bepridil抑制内整流钾电流（I (K1)）的短期效应为IC50为17 μ m， Bepridil在IC50为2.7 μ m的培养基中作用24小时也降低了新生儿心肌细胞的I （K1）。钙调素抑制剂（W-7）和钙调素激酶II抑制剂（KN93）以同样的方式作用24小时也降低了I （K1）。这表明长期应用贝普利地尔比短期应用贝普利地尔通过抑制心肌细胞钙调蛋白激酶II途径更有效地抑制I （K1）。
Bepridil is an effective antiarrhythmic drug on supraventricular and ventricular arrhythmias, and inhibitor of calmodulin. Recent investigations have been elucidating that bepridil exerts antiarrhythmic effects through its acute and chronic application for patients. The aim of this study was to identify the efficacy and the potential mechanism of bepridil on the inward-rectifier potassium channel in neonatal rat cardiomyocytes in acute- and long-term conditions. Bepridil inhibited inward-rectifier potassium current (I (K1)) as a short-term effect with IC50 of 17 mu M. Bepridil also reduced I (K1) of neonatal cardiomyocytes when applied for 24 h in the culture medium with IC50 of 2.7 mu M. Both a calmodulin inhibitor (W-7) and an inhibitor of calmodulin-kinase II (KN93) reduced I (K1) when applied for 24 h as a long-term effect in the same fashion, suggesting that the long-term application of bepridil inhibits I (K1) more potently than that of the short-term application through the inhibition of calmodulin kinase II pathway in cardiomyocytes.