ENHANCEMENT BY AN ANTAGONIST OF TRANSMITTER RELEASE FROM FROG MOTOR NERVE TERMINALS

The effect of Ba²⁺ on the synchronous release of acetylcholine from frog motor nerve terminals was studied by conventional electrophysiological techniques. When Ca²⁺ and Ba²⁺ were the only divalent cations in the bathing fluid, Ba²⁺ caused a presynaptic reduction in the amplitude of the endplate potential (e.p.p.). This effect was surmountable by increasing the Ca²⁺ concentration. The affinity constant (K_A) for Ba²⁺, calculated on the assumption that Ba²⁺ is a competitive inhibitor of the agonist, Ca²⁺, was 1.1 + 0.4 mM⁻¹ (mean + s.e.mean, n = 8). When e.p.ps were depressed by the addition of 1 mm Mg²⁺, addition of Ba²⁺ (1 to 3 mm) caused either a further presynaptic depression of moderate magnitude or had no additional effect. When e.p.p.s were depressed with [Mg²⁺] > 2 mm, addition of Ba²⁺ > 0.9 mm enhanced the e.p.p. amplitude by a presynaptic mechanism. The interaction of the divalent cation antagonists Mg²⁺ and Ba²⁺ with the agonist, Ca²⁺ is discussed. It is demonstrated that a model which considers the nonequilibrium, kinetic properties of binding can be used to describe interactions between divalent cations at the external surface of the motor nerve ending. 1978 British Pharmacological Society