title: Electrophysiological effects of bethanidine sulfate on canine cardiac Purkinje fibers and ventricular muscle cells.
abstract: Bethanidine sulfate is a congener of bretylium tosylate, which has been reported to have antiarrhythmic and antifibrillatory effects. We studied the effects of bethanidine on transmembrane potentials recorded from canine Purkinje fibers and ventricular muscle cells, using standard microelectrode techniques. Normal Purkinje fibers were exposed to bethanidine (10-80 mg/L) for 30-40 min. Bethanidine produced dose-dependent decreases in the maximal rate of depolarization (MRD) and over-shoot of phase 0, but did not affect maximum diastolic potential (MDP). Action potential plateau duration (APD, to -60 mV) was decreased by bethanidine at all cycle lengths of stimulation between 1,000 and 300 ms. Bethanidine depressed the membrane responsiveness curve, and its effects on MRD showed marked use dependence. In ventricular muscle cells, bethanidine 20 mg/L decreased MRD but did not affect MDP or APD. The rate of normal automaticity in Purkinje fibers with MDPs greater than -85 mV was increased to 21.5 +/- 5.6 beats/min after exposure to bethanidine (10 mg/L for 30 min) from control values of 10.2 +/- 5.3 beats/min. Abnormal automaticity (MDPs = -40 to -60 mV) was induced in Purkinje fibers by superfusion with Tyrode solution containing 0.25 mM BaCl2; this activity also was accelerated after exposure to bethanidine 10 mg/L. The effects of bethanidine on automaticity are similar to those of bretylium, and may be caused by release of endogenous catecholamines. In contrast, the effects of bethanidine on action potentials of normal (driven) Purkinje fibers are markedly different from those of bretylium, and resemble those of lidocaine after 30-60 min of exposure.
authors.forename: K H
authors.initials: KH
authors.lastname: Dangman
authors.forename: D S
authors.initials: DS
authors.lastname: Miura
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001627:Bethanidine / Q000494:pharmacology*; D001950:Bretylium Tosylate / Q000494:pharmacology; D003971:Diastole; D004285:Dogs; D006146:Guanidines / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles; D066298:In Vitro Techniques; D011690:Purkinje Fibers / Q000187:drug effects*
chemical_list: D006146:Guanidines; D001950:Bretylium Tosylate; D001627:Bethanidine