Bethanidine increased Na+ and Ca2+ currents and caused a positive inotropic effect in heart cells.
The effects of bethanidine sulphate, a pharmacological analog of the cardiac antibrillatory drug, bretylium tosylate, were studied on action potentials (APs) and K+, Na+, and Ca2+ currents of single cultured embryonic chick heart cells using the whole-cell current clamp and voltage clamp technique. Extracellular application of bethanidine (3 X 10(-4) M) increased the overshoot and the duration of the APs and greatly decreased the outward K+ current (IK) and potentiated the inward fast Na+ currents (INa) and the inward slow calcium current (ICa). However, intracellular introduction of bethanidine (10(-4) M) blocked INa. In isolated atria of rat, bethanidine increased the force of contraction in a dose-dependent manner. These findings suggest that when applied extracellularly, bethanidine exerts a potentiating effect on the myocardial fast Na+ current and slow Ca2+ current and an inhibitory effect of IK. The positive inotropic effect of bethanidine could be due, at least in part, to an increase of Ca2+ influx via the slow Ca2+ channel and the Na-Ca exchange. It is suggested that the decrease of IK by bethanidine may account for its antifibrillatory action.
Bkaily
G
G
Department of Physiology and Biophysics, Faculty of Medicine, University of Sherbrooke, Qué., Canada.
Payet
M D
MD
Benabderrazik
M
M
Renaud
J F
JF
Sauvé
R
R
Bacaner
M B
MB
Sperelakis
N
N
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001627:Bethanidine / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D006146:Guanidines / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology; D051381:Rats; D012964:Sodium / Q000502:physiology*; D013268:Stimulation, Chemical
D006146:Guanidines; D012964:Sodium; D002118:Calcium; D001627:Bethanidine