Sulfonylureas blockade of neural and cardiac HERG channels
Sulfonylureas blockade of neural and cardiac HERG channels
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DOI：
10.1016/s0014-5793(98)01444-6
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发表时间：
1998-11-27
期刊：
影响因子：
3.5
通讯作者：
Wanke, E
中科院分区：
文献类型：
--
作者：
Rosati, B;Rocchetti, R;Wanke, E
人类ether-a-go-go-related基因（herg）编码的K+电流（I-HERG）在心脏兴奋性和神经元中分别通过促进动作电位复极和尖峰频率适应而发挥重要作用。在本文中，我们表明，I-HERG，记录在神经母细胞瘤细胞和豚鼠心室肌细胞，可逆地抑制K-ATP通道阻滞剂格列本脲（IC 50 = 74 μ M）。还评价了格列本脲阻滞的电压依赖性和使用依赖性。另一种磺酰脲类药物格列美脲在阻断I-HERG方面效果较差。本研究的结果与解释格列本脲对细胞电生理学的影响相关，并表明磺脲类口服降糖治疗可能导致医源性QT间期延长和相关心律失常。(C)1998年欧洲生物化学学会联合会。
The human ether-a-go-go-related gene (herg) encodes a K+ current (I-HERG) which plays a fundamental role in heart excitability and in neurons by contributing to action potential repolarization and to spike-frequency adaptation, respectively. In this paper we show that I-HERG, recorded in neuroblastoma cells and guinea-pig ventricular myocytes, was reversibly inhibited by the K-ATP channel blocker glibenclamide (IC50 = 74 mu M). The voltage and use dependence of glibenclamide blockade mere also evaluated. Another sulfonylurea, glimepiride, had less effective results in blocking I-HERG. The findings of this study are relevant to the interpretation of glibenclamide effects on cellular electrophysiology and suggest that oral antidiabetic therapy with sulfonylureas may contribute to iatrogenic QT prolongation and related arrhythmias. (C) 1998 Federation of European Biochemical Societies.