Elevated tonicity increases miniature end-plate potential frequency during tetanic stimulation at frog neuromuscular junction in low calcium and in manganese saline solutions.

We have followed the increase in miniature end-plate potential (MEPP) frequency that occurs during tetanic stimulation of the motor nerve in low Ca2+ and in Mn2+ saline solutions. During stimulation in either solution the frequency rises over the first minutes to reach an asymptote. In low Ca2+ solutions, hypertonicity increases the rate at which the MEPP frequency rises. Raising the [Mn2+] also increases the rate at which the MEPP frequency rises and elevates the level of the asymptote. The data are interpreted by using a model in which quantal release frequency is proportional to the [( Ca2+])n in the nerve terminal; the model specifically includes the [Ca2+] in the terminal before stimulation. There is evidence that hypertonic solutions elevate the [Ca2+]i. We suggest that the effects of tonicity increases can be accounted for solely by the rise in [Ca2+]i before the beginning of the tetanus. If the number of Ca2+ cooperating in release, n, is 4, then with each stimulus there must be an increase in Ca2+ influx. If the value of n is higher, for example 50, the amount of Ca2+ entering with each stimulus is roughly constant. The data from the Mn2+ experiments also suggest than n may be greater than 4. It is pointed out that for exocytotic transmitter release, many Ca2+ ions may cooperate in the release process, so high values of n are not unreasonable.