Anticholinergic effects of artemisinin, an antimalarial drug, in isolated guinea pig heart preparations.
Concern has been growing about the cardiac toxicity of antimalarial drugs. Artemisinin, a unique type of antimalarial drug originating from a Chinese medicinal plant, has minimal adverse effects, but it has been reported to inhibit delayed rectifier potassium current, a voltage-gated potassium current. However, no studies have been published concerning the effect of artemisinin on ligand-gated potassium currents. Therefore, in the present study, we examined the influence of artemisinin on the acetylcholine receptor-operated potassium current (IK.ACh), a ligand-gated potassium current, in guinea pig atrial myocytes using a patch clamp technique. Artemisinin (1 to 300 microM) inhibited I(K.ACh) induced by extracellular application of both carbachol (1 microM) and adenosine (10 microM) and that induced by intracellular loading of GTPgammaS (100 microM) in a concentration-dependent manner. Artemisinin inhibited carbachol-induced, adenosine-induced, and GTPgammaS-activated IK.ACh within almost the same concentration range. In left atria, artemisinin (1 to 100 microM) partially reversed the shortening of action potential duration induced by carbachol in a concentration-dependent manner. Carbachol-induced negative inotropic action in left atria was also inhibited by artemisinin (10 to 300 microM). In conclusion, we suggest that the anticholinergic action of artemisinin is mediated through inhibition of IK.ACh via inhibition of the muscarinic potassium channel and/or associated GTP-binding proteins.
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine and Animal Sciences, Kitasato University, Towada, Aomori 034-8628, Japan. hara@vmas.kitasato-u.ac.jp
Yukio
Y
Hara
Hideyuki
H
Yamawaki
Masami
M
Shimada
Kiyohiro
K
Okada
Toshiki
T
Tanai
Daiki
D
Ichikawa
Kimihito
K
Miyake
Keiichiro
K
Kizaki
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D016279:Atrial Function, Left / Q000187:drug effects; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism
D000962:Antimalarials; D037621:Artemisinins; D018680:Cholinergic Antagonists; D011950:Receptors, Cholinergic; D011188:Potassium