The action of cobalt ions on neuromuscular transmission in the frog

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Abstract
1. Cobalt ions, in concentrations of 0·05‐2 m M, block neuromuscular transmission in the frog sartorius muscle.2. The reduction in the e.p.p. amplitude produced by Co2+ 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 Co2+ may be antagonized by elevation of the external Ca2+ concentration. It is suggested that the antagonism between Co2+ and Ca2+ is competitive in nature.4. The mean dissociation constant for Co2+ and its hypothetical membrane complex was found to be 0·18 m M. On this basis, it is concluded that Co2+ is about 20 times more potent than Mg2+ in suppressing evoked transmitter release.5. In contrast to the inhibitory action on evoked release, Co2+ increases spontaneous transmitter release. However, concentrations of Co2+ 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.