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- Title
Influence of Extracellular K<sup>+</sup> Concentrations on Quinidine-induced K<sup>+</sup> Current Inhibition in Rat Ventricular Myocytes.
- Authors
HIROTA, MICHIKO; OHTANI, HISAKAZU; HANADA, ERIKA; SATO, HITOSHI; KOTAKI, HAJIME; UEMURA, HIROKO; NAKAYA, HARUAKI; IGA, TATSUJI
- 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 (IK), the transient outward current (Ito), and the inward rectifier potassium current (IK1), as measured in isolated rat ventricular cells using patch-clamp techniques. Concentration-dependent effects of quinidine on IK, Ito, and IK1 were evaluated under both normal ([K+]o = 5.4 mM) and hypokalaemic ([K+]o = 3.5 mM) conditions. In contrast to both IK and Ito, which were barely influenced by changes in [K+]o, IK1 was significantly inhibited by hypokalaemia. Furthermore, while quinidine suppressed both IK and Ito 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 (IK), and 17.6 and 17.3 μM (Ito). Although higher concentrations of quinidine were required to inhibit IK1, 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 IK, Ito and IK1 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 hypokalaemia does not affect IK or Ito, it can inhibit IK1 and can result in QT prolongation in-vivo.
- Publication
Journal of Pharmacy & Pharmacology, 2000, Vol 52, Issue 1, p99
- ISSN
0022-3573
- Publication type
Article
- DOI
10.1211/0022357001773571