THE EFFECTS OF VERAPAMIL ON METABOLISM AND CONTRACTILITY OF THE TOAD SKELETAL MUSCLE

¹ Departments of Ophthalmology and Pharmacology, Mount Sinai School of Medicine of the City University of New York, New York, New York

When the potassium concentration in the Ringer's solution bathing toad skeletal muscle is raised, oxygen consumption increases 3- to 6-fold ("Solandt effect"). This response is antagonized by verapamil at concentrations as low as 10^-6 M. This antagonism does not reflect a general depression of the resting basal metabolic rate nor is it seen when oxygen consumption is stimulated by 2,4-dinitrophenol or caffeine. The inhibitory effect of verapamil on the Solandt effect is not decreased in the presence of elevated calcium levels. Procaine also reduces the Solandt effect but propranolol,succinylcholine and tubocurarine do not affect it. Acetylcholine contracts toad skeletal muscle and this response is also antagonized by verapamil (as low as 10^-6 M) in a noncompetitive manner. This effect could be reversed upon washing the muscle in fresh Ringer's solution. Elevated calcium (10 mM) concentrations did not reduce the antagonism of verapamil to acetylcholine-induced contractures. Contractures in response to potassium or caffeine were unaffected by verapamil (10^-4 M). The effects of verapamil on the contractility of skeletal muscle were compared to the effects of procaine and tubocurarine. Procaine inhibits the effect of caffeine but not acetylcholine while tubocurarine (like verapamil) blocks the action of acetylcholine but not caffeine. It is suggested that verapamil has a neuromuscular-blocking effect. Its antagonism to the Solandt effect cannot be related to this and appears to represent an independent action.