DEPRESSION BY CALCIUM OF SPONTANEOUS TRANSMITTER RELEASE AT THE MAMMALIAN NEUROMUSCULAR-JUNCTION

The effect of extracellular calcium on the frequency of miniature end-plate potentials (MEPPs) at the rat neuromuscular junction was studied using 5 different concentrations of K+ (2.5, 5, 10, 15 and 20 mM). At low and normal levels of K+ (2.5 and 5 mM), incremental increase of Ca2+ concentration (0.1, 0.5, 1, 2, 3, 4, 7 and 10 mM) produced a slight monotonic increase in MEPP frequency. In 10 or 15 mM-K+, the frequency of MEPPs increased monotonically as Ca2+ concentration was raised from 0.1 to 4 mM, but was unaltered or declinedslightly with further increase of Ca2+ concentration. In 20 mM-K+, the frequency reached its maximum at 1 mM-Ca2+ and progressively decreased as Ca2+ concentration was increased to 10 mM. Thus, the relationship between Ca2+ concentration and MEPP frequency was monotonic at the lower levels of K+ but became distinctly non-monoonic with increased K+. This non-monotonic effect of Ca2+ is consistent with the hypothesis that there are two opposing effects of increasing Ca2+ concentration on transmitter release: (i) an increased Nernst equilibrium potential for Ca2+ which causes an increase in Ca2+ influx and a consequent rise in MEPP frequency and (ii) increased electrostatic screening of negative surface charges near Ca2+ channels which produces an effective hyperpolarization across the channels and a consequent decrease in Ca2+ influx. © 1979.