Volume 11, Issue 2 pp. 112-116

Antimalarial Drugs Inhibit the Acetylcholine-Receptor-Operated Potassium Current in Atrial Myocytes

Yukio Hara PhD

Yukio Hara PhD

Department of Veterinary Pharmacology, School of Veterinary Medicine and Animal Sciences, Kitasato University, Towada, Aomori, Japan

Search for more papers by this author
Keiichiro Kizaki PhD

Keiichiro Kizaki PhD

Department of Veterinary Pharmacology, School of Veterinary Medicine and Animal Sciences, Kitasato University, Towada, Aomori, Japan

Search for more papers by this author
First published: 09 August 2002
Citations: 2
Yukio Hara, Department of Veterinary Pharmacology, School of Veterinary Medicine and Animal Sciences, Kitasato University, Higashi 23 ban-cho 35-1, Towada, Aomori 034-8628, Japan. Email: [email protected]

Abstract

Background: It has been reported that halofantrine, an antimalarial drug, was associated with electrocardiographic prolongation of the QT interval and ventricular arrhythmias. Inhibition of the delayed rectifier potassium channel, a voltage-gated potassium channel, by halofantrine was the likely underlying cellular mechanism for this cardiotoxicity. However, influences of anti­malarial drugs on the ligand-gated potassium channels have not been well-documented. The influences of three different antimalarial drugs, chloroquine, primaquine and pyrimethamine, on the acetylcholine-receptor-operated potassium current (IK.ACh), a ligand-gated potassium current, were compared with the effect of quinidine in isolated guinea pig atrial myocytes using patch-clamp techniques.

Methods: The whole-cell patch-clamp method was used in the present study. The IK.ACh was induced by extracellular application of carbachol (1 µmol/L) or intracellular loading of guano­sine 5"-O-(3-thiotriphosphate) GTPγS (100 µmol/L) in acutely isolated guinea pig atrial myocytes.

Results: The IK.ACh induced by carbachol was inhibited by chloroquine, primaquine, pyrimethamine and quinidine in a concentration-dependent manner, and the concentrations required to produce 50% of the maximal inhibitory effect (IC50 values) were 0.7, 2.5, 12 and 1.8 µmol/L, respectively. These drugs also inhibited the intracellular GTPγS-activated IK.ACh, and the IC50 values were 0.8, 13, 19 and 21 µmol/L, respectively.

Conclusions: Chloroquine and pyrimethamine may inhibit IK.ACh by interacting with the muscarinic potassium channel itself and/or associated guanosine 5"-triphosphate-binding proteins, whereas primaquine and quinidine may mainly inhibit the current by the blockade of the muscarinic receptors. These results indicate that antimalarial drugs exert anticholinergic effects via different molecular mechanisms. (Heart, Lung and Circulation 2002; 11: 112−116)

The full text of this article hosted at iucr.org is unavailable due to technical difficulties.