Actions of flunarizine dihydrochloride on the electrical activity of isolated guinea-pig papillary muscle and rabbit sino-atrial node.
Effects of flunarizine on electrophysiological properties of isolated guinea-pig papillary muscles and rabbit sino-atrial nodes were examined using conventional microelectrode and double-microelectrode voltage clamp methods. Although flunarizine did not affect the maximum rate of rise of the action potential (Vmax) in fast response fibers, the compound depressed the slow action potentials of K+-depolarized papillary muscle (at above 10 microM) and reduced the automaticity of sino-atrial node (at above 3 microM). In voltage clamp experiments, flunarizine selectively suppressed the slow inward current of sino-atrial node specimens. It is concluded that relatively high concentrations of flunarizine directly modify the electrical activity of isolated mammalian myocardium via a suppression of Ca2+ influx through the cell membrane.
Kotake
H
H
First Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan.
Kinugawa
T
T
Hirai
S
S
Nawada
T
T
Takami
T
T
Hasegawa
J
J
Mashiba
H
H
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005444:Flunarizine / Q000494:pharmacology*; D006168:Guinea Pigs; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects* / Q000502:physiology
D005444:Flunarizine