Facilitatory effects of 4-aminopyridine on strontium-mediated evoked and delayed transmitter release from motor nerve terminals.

The effect of 4-aminopyridine (4-AP) on Sr-mediated evoked and delayed transmitter release at the frog neuromuscular junction was examined using conventional electrophysiological techniques. 4-AP (5-50 microM) increased transmitter release evoked in response to conducted nerve impulses or to electrotonic depolarization of tetrodotoxin (TTX)-treated motor nerve terminals. Spontaneous quantal transmitter release was not affected by the drug as judged by the lack of effect on miniature end-plate potentials (MEPPs) frequency. However, 4-AP (10-20 microM) markedly enhanced the frequency of MEPPs appearing during conducted low rate repetitive nerve impulses or single electrotonic depolarization of TTX-blocked nerve terminals. The results suggest that 4-AP increases the influx of Sr2+ into nerve terminals in a way that modifies its sequestration and removal by the subcellular elements of the terminal.