Cumulative and persistent effects of nerve terminal depolarization on transmitter release.

1. Following focal depolarization of rat motor nerve terminals there could often be observed an ;after-discharge' of m.e.p.p.s with transient frequencies of up to 1000/sec. This after-discharge was graded with intensity and duration of the previous depolarization.2. Following pulses which were relatively short (about 1 sec) and not too large (< -100 mV local extracellular potential field) the logarithm of m.e.p.p. frequency fell exponentially. With larger or longer pulses there was a tail to the after-discharge which could persist for several minutes.3. M.e.p.p. frequency during an after-discharge was not inhibited appreciably by nerve terminal hyperpolarization, raised [Ca] (8 mM) or lowered pH.4. Measured as a multiplication of spontaneous m.e.p.p. frequency after-discharge was depressed in solution containing no Ca(2+) and added 1 mM-MgEDTA but equal in 0.125 mM-Ca(2+) or 2 mM-Sr(2+) to that in 2 mM-Ca(2+) or 8 mM-Ca(2+).5. During an after-discharge the multiplication of m.e.p.p. frequency by focal nerve terminal depolarization or raised K(+) was reduced. This phenomenon was termed ;uncoupling'.6. It was concluded that the after-discharge is not caused by a persistent rise of K(+) concentration in the synaptic cleft, nor by a maintained nerve terminal depolarization.7. In preparations depolarized by raised K(+) m.e.p.p. frequency during a relatively small focal depolarizing pulse rose continuously, after an initial rapid rise, and after the pulse there was a tail of increased m.e.p.p. frequency. The magnitude of the rise during the pulse and the tail after it were similar on, a logarithmic basis; during both processes the logarithm of m.e.p.p. frequency usually followed (approximately) an exponential time course.8. The relative magnitude of the slow effect of depolarization, as compared with the fast effect, was increased by lowering [Ca] or increasing [Mg], and the slow effect of depolarization in contrast to the fast effect was found to exist in the presence of Ca reduced to about 10(-7)M, but only during pulses. At this [Ca] there was no rapid response to depolarization. At [Ca] about 10(-10)M, there was no response at all of m.e.p.p. frequency to nerve terminal depolarization.9. The results are discussed, and compared with similar data referring to ;facilitation' and ;post-tetanic potentiation'. It is concluded that these and the slow effect of depolarization represent the same phenomenon, a response of the transmitter release system which can be distinguished from the fast response in terms of ionic requirement as well as time course.