Influence of extracellular K+ concentrations on quinidine-induced K+ current inhibition in rat ventricular myocytes

Michiko Hirota, Hisakazu Ohtani, Erika Hanada, Hitoshi Sato, Hajime Kotaki, Hiroko Uemura, Haruaki Nakaya, Iga Tatsuji

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11 Citations (Scopus)

Abstract

Hypokalaemia is one of the important risk factors for development of torsades de pointes. We recently reported that hypokalaemia increased the electrocardiographic QT interval in rats treated with quinidine, but did not alter the arrhythmogenic potency of quinidine. In this study, we have investigated the influence of extracellular potassium concentration ([K+](o)) on the inhibition of several types of cardiac potassium currents by quinidine. Such types of currents include the delayed rectifier potassium current (I(K)), the transient outward current (I(to)), and the inward rectifier potassium current (I(K1)), as measured in isolated rat ventricular cells using patch-clamp techniques. Concentration-dependent effects of quinidine on I(K), I(to), and I(K1) were evaluated under both normal ([K+](o) = 5.4 mM) and hypokalaemic ([K+](o) = 3.5 mM) conditions. In contrast to both I(K) and I(to), which were barely influenced by changes in [K+](o), I(K1) was significantly inhibited by hypokalaemia. Furthermore, while quinidine suppressed both I(K) and I(to) in a concentration-dependent manner, the inhibitory potency of quinidine on these currents was not influenced by changes in [K+](o). The respective normal and hypokalaemic IC50 values for quinidine were 11.4 and 10.0 μM (I(K)), and 17.6 and 17.3 μM (I(to)). Although higher concentrations of quinidine were required to inhibit I(K1), the inhibitory potency of quinidine was also found to be insensitive to changes in [K+](o). Thus, in rats, the inhibitory potency of quinidine for the K+ current-types I(K), I(to) and I(K1) is barely influenced by changes in [K+](o). These findings are consistent with our previous report showing that the QT-prolonging potency of quinidine was not altered under hypokalaemic conditions. However, whilst hypokalemia does not affect I(K) or I(to), it can inhibit I(K1) and can result in QT prolongation in-vivo.

Original languageEnglish
Pages (from-to)99-105
Number of pages7
JournalJournal of Pharmacy and Pharmacology
Volume52
Issue number1
DOIs
Publication statusPublished - 2000 Jan
Externally publishedYes

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ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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