Inhibition of cardiac inward-rectifier K+ current by terodiline

被引：6

作者：

Jones, SE

Kasamaki, Y

Ogura, T

Shuba, LM

McCullough, JR

McDonald, TF ^{[1
]}

机构：

[1] Dalhousie Univ, Dept Physiol & Biophys, Halifax, NS B3H 4H7, Canada

[2] Sepracor, Marlborough, MA 01752 USA

[3] Nihon Univ, Sch Med, Dept Internal Med 2, Itabashi Ku, Tokyo 173, Japan

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1999年 / 370卷 / 03期

基金：

英国医学研究理事会;

关键词：

papillary muscle; action potential; ventricular myocyte guinea pig; K+ current; Ca2+ current;

D O I：

10.1016/S0014-2999(99)00130-2

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The antispasmodic agent terodiline has cardiotoxic effects that include QT lengthening. To determine whether inhibition of inwardly-rectifying K+ current (I-K1) might be a factor in the cardiotoxicity, we measured I-K1 in guinea pig ventricular myocytes. Terodiline reduced outward I-K1 with an IC50 of 7 mu M; maximal reduction was 60% with 100-300 mu M concentration. Inhibition was independent of current direction, and persisted after removal of the drug. Terodiline (3-5 mu M) lengthened action potentials in guinea pig papillary muscles by ca. 10%, primarily by slowing phase 3 repolarization; higher concentrations abbreviated the plateau and markedly slowed late repolarization. Terodiline washout provoked an extra lengthening, consistent with persistent inhibition of I-K1 and rapid recovery of net inward plateau current. The results suggest that inhibition of I-K1 is a likely factor in the cardiotoxicity of the drug. (C) 1999 Elsevier Science B.V. All rights reserved.

引用

页码：319 / 327

页数：9

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