Sulfonylureas blockade of neural and cardiac HERG channels

FEBS Letters

Wanke, Enzo¹  Zaza, Antonio¹  Rosati, Barbara¹  Rocchetti, Marcella¹ 

[1] Dipartimento di Fisiologia e Biochimica Generali, Università degli Studi di Milano, Via Celoria 26, 20133 Milan, Italy

关键词: Glibenclamide;    K+ channel;    HERG channel;    Cardiac cell;   

DOI  :  10.1016/S0014-5793(98)01444-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 μM). The voltage and use dependence of glibenclamide blockade were 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.

【 授权许可】

Unknown