The inhibitory effect of manganese on transmitter release at the neuromuscular junction of the toad.

1. Manganese, at low concentrations (0.5-2.0 mM), blocks neuromuscular transmission in toads. Endplate potentials (e.p.ps) are reduced in amplitude but the amplitude of miniature endplate potentials (m.e.p.ps) is, if anything, increased.2. The release of transmitter by an action potential is reduced in solutions containing Mn, but is still well described by the Poisson equation.3. Log-log plots of e.p.p. quantal content (m) against [Ca] have a mean gradient of 3.73, and a model based on the co-operative action of four calcium ions in excitation-secretion coupling, and competitive inhibition by Mn, was constructed. The model, with its exponent of 4, is shown in fact to predict gradients of less than four for log-log plots of m against [Ca].4. The assumption of competitive inhibition by Mn was supported by modified Lineweaver-Burk plots of m(-(1/4)) against 1/[Ca]. The mean dissociation constants for Ca and Mn were 1.3 mM and 0.15 mM respectively. From the model, an upper estimate of the density of calcium ;receptor sites' of 30 per square micron of nerve terminal was obtained.5. In contrast to its inhibitory effect on evoked release, Mn increases the spontaneous release of transmitter. It is suggested that Mn may increase m.e.p.p. frequency by releasing Ca from an intracellular store.