How elevated extracellular Ca2+ inhibits quantal acetylcholine release at frog neuromuscular junctions in high K+.

It is known that when end-plates partially depolarized in elevated [K+]o are exposed to an increase in [Ca2+]o there is a decrease in the min.e.p.p. frequency. Two hypotheses to account for the observations are: (1) a rise in [Ca2+]i inhibits m.e.p.p. generation; (2) the divalent metal ions decrease the surface potential on the nerve terminal and thereby increase the voltage drop in the membrane, depressing Ca2+ influx. In preparations in elevated [K+]o and [Ca2+]o, the m.e.p.p. frequency is increased further by additional depolarization, by Ca2+ ionophores, by increasing the tonicity of the extracellular solution, and by replacing the NaCl in the external solution with LiCl. All of these treatments are thought to further increase [Ca2+]i. Ba2+ and Sr2+ produce effects like Ca2+. However, if the increase in [Ca2+]o is compensated by a decrease [Na+]o sufficient to leave the surface potential unchanged, there is little alteration in m.e.p.p. frequency.