当前位置： SCI文献检索 > JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY期刊下所有文献 > Evidences of antagonism between amiodarone and triiodothyronine on the K+ channel activities of cultured rat cardiomyocytes.

Evidences of antagonism between amiodarone and triiodothyronine on the K+ channel activities of cultured rat cardiomyocytes.

Abstract：

:Effects of acute and chronic treatments with amiodarone, both in the presence and the absence of exogenous triiodothyronine (T3), on repolarizing outward K+ currents were investigated by patch-clamp technique in cultured newborn rat ventricular cells. Acute exposure to amiodarone dose-dependently inhibited the transient outward (Ito IC50 = 4.9 microM) and the steady-state outward (IK, IC50 = 6.3 microM) K4 currents. The dose-response curve of this acute inhibitory action was unaffected by the presence of T3. When amiodarone was applied chronically. 72-h exposure to a low dose of the drug (1 microM) significantly decreased the current densities of Ito and I kappa for the cells cultured in a serum-supplemented medium containing 0.12 nM T3. In a serum-free medium without T3o chronic amiodarone treatment revealed null effect on either Ito or IK. In addition, 72-h in-vitro treatment with Ti enhanced the current densities of both Ito (EC50 = 0.13 nM) and I kappa (EC50 = 0.33 nM). Concentration-response analysis indicated that amiodarone (1 microM) showed competitive inhibition towards the action of T3 on Ito but noncompetitive inhibition towards the action of T3 on IK. These results suggest that different ionic mechanisms are produced by acute and long-term treatments with amiodarone. The latter showed T3-dependent inhibition of cardiac Ito and IK. When chronically administered, amiodarone may antagonize T3 and thereby counteract its hormonal effect on K+ channels. This implies that, at the myocyte level, antagonism of the action of thyroid hormones in K+ channel activities may contribute to the cardiac effects of chronic amiodarone therapy.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Guo W,Kamiya K,Toyama J

doi

10.1006/jmcc.1996.0305

subject

Has Abstract

pub_date

1997-02-01 00:00:00

pages

617-27

issue

2

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(96)90305-3

journal_volume

29

pub_type

杂志文章

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