Mode of action of veratridine on perfused frog ventricle

Veratridine exerts a biphasic action on the perfused frog ventricle. The initial immediate response is a depression, which is maximal at 10(-10) M. The initial depression is followed by a late potentiation of contraction which is maximal at 10(-6) to 10(-7) M veratridine. Reduction of external calcium from 1.0 mM to 0.5 mM prevents the initial depression and allows only the potentiation of contraction to be observed. The force of contraction in 0.5 mM Ca2+ is increased by veratridine to 200% of the contraction observed at 1.0 mM Ca2+. The primary site for the enhancement of contraction in the frog ventricle by veratridine is the adrenergic nerve fibers whose increase in excitability leads to an increase in epinephrine release. The beta blocker sotalol at 10(-6) M prevents the increase in contractility by veratridine in 0.4 mM Ca2+. Calcium itself depressed potentiation of contractility by veratridine by stabilizing the adrenergic nerves and antagonizing the labilizing action of veratridine. The mode of action of veratridine on the frog ventricle is attributed to the enhancement of transmitter release from cholinergic and adrenergic nerve fibers.