Effect of 4-aminopyridine on transmitter release in synaptosomes

The effect of 4-aminopyridine (4-AP) on the release of labeled transmitters in mouse brain synaptosomes was studied in a superfusion system. 4-AP at microM concentrations notably stimulated the spontaneous release of labeled GABA and glutamate, and of acetylcholine (ACh) derived from tritiated choline. No effects on the release of labeled alpha-aminoisobutyric acid were observed. The stimulation of GABA and ACh release was dependent on the presence of Ca2+ in the superfusion media, whereas the effect on glutamate release was more variable and no clear Ca2+-dependence was observed. In contrast to these results, 4-AP did not have any effect on the release of the above transmitters stimulated by K+-depolarization in the presence of Ca2+. These results are discussed in terms of the possible participation of Ca2+ in the action of 4-AP on spontaneous transmitter release in isolated nerve endings.