The action of cobalt ions on neuromuscular transmission in the frog.

1. Cobalt ions, in concentrations of 0.05-2 mM, block neuromuscular transmission in the frog sartorius muscle.2. The reduction in the e.p.p. amplitude produced by Co(2+) is due to a decrease in the amount of transmitter released by a nerve impulse (mean quantum content). This reduction is associated with little change in the resting membrane potential of the muscle fibre or in the mean amplitude of spontaneous m.e.p.p.s.3. The reduction in evoked transmitter release produced by Co(2+) may be antagonized by elevation of the external Ca(2+) concentration. It is suggested that the antagonism between Co(2+) and Ca(2+) is competitive in nature.4. The mean dissociation constant for Co(2+) and its hypothetical membrane complex was found to be 0.18 mM. On this basis, it is concluded that Co(2+) is about 20 times more potent than Mg(2+) in suppressing evoked transmitter release.5. In contrast to the inhibitory action on evoked release, Co(2+) increases spontaneous transmitter release. However, concentrations of Co(2+) 20-60 times greater than those which decrease the e.p.p. amplitude are needed to produce a significant increase in m.e.p.p. frequency.