On the effect of calcium on the frequency of miniature end-plate potentials at the frog neuromuscular junction.

1. The effect of the extracellular Ca concentration on the frequency of miniature end-plate potentials (min. e.p.p.s) at the frog neuromuscular junction was studied. 2. In saline containing elevated K (5 or 11 mM), the frequency of min. e.p.p.s increased as Ca concentration was increased from 0-1 to 1-3 mM. However, with further increases of Ca concentration up to 10 mM, min. E.P.P. frequency declined. 3. In saline containing the normal concentration of K (2 mM), increasing Ca concentration from 0-1 to 10 mM produced a slight, monotonic increase in min. e.p.p. frequency. 4. The non-monotonic effect of Ca on min. e.p.p. frequency in preparations depolarized by elevated K is consistent with the existence of two opposing effects of Ca on transmitter release. Firstly, raising the external concentration of Ca increases the electrochemical potential for Ca entry, which tends to increase Ca influx and transmitter release. Secondly, increasing external Ca concentration increases electrostatic screening of fixed negative charges on the outer surface of the nerve terminal membrane. Such an increase in screening of charges near voltage-sensitive Ca gates would produce a hyperpolarization across the gates and they would tend to close, an effect which would tend to decrease Ca influx. The monotonic increase in min. e.p.p. frequency with increasing Ca concentration in 2 mM-K is consistent with the voltage insensitivity of the Ca gates at potentials close to the normal resting potential.