Sulfonylureas blockade of neural and cardiac HERG channels.

Abstract:

: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 microM). 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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Rosati B,Rocchetti M,Zaza A,Wanke E

doi

10.1016/s0014-5793(98)01444-6

subject

Has Abstract

pub_date

1998-11-27 00:00:00

pages

125-30

issue

1-2

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(98)01444-6

journal_volume

440

pub_type

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