4-Aminopyridine differentially affects the spontaneous release of radiolabelled transmitters from rat brain slices in vitro

4-Aminopyridine increased the release of [H-3]noradrenaline from dorsal hippocampus slices in vitro in a concentration-dependent manner. When the slices were exposed to 4-aminopyridine for 5 min, the overflow of radioactivity returned to pre-exposure values within 20-25 min. When the exposure of the slices was continued, a sustained enhancement of the release of [H-3]noradrenaline was observed for the duration of the exposure. 4-Aminopyridine, 10(-4) M, had an effect of similar magnitude, or an even more pronounced effect, on the release of [H-3]catecholamine from cortex, septum, periaqueductal gray and striatum slices. The effects of the compound on the release of [H-3]5-hydroxytryptamine and [C-14]acetylcholine were less pronounced. At this concentration 4-aminopyridine had no effect on the release of [H-3]D-aspartate from hippocampus or septum slices, whereas the effect on the release of this transmitter in striatal slices was marginal. The effect of 4-aminopyridine on the release of [3H]noradrenaline in hippocampus slices was largely dependent on the presence of Ca2+ in the superfusion medium. This was also the case for the effect on the release of [H-3]noradrenaline from preloaded dorsal hippocampus synaptosomes. In the presence of nitrendipine the effect of 4-aminopyridine was dose-dependently reduced, but the maximal reduction, at a nitrendipine concentration of 10(-4) M, was only 40%. Cd2+ completely abolished the effect of 4-aminopyridine on the release of [H-3]noradrenaline. These results confirm that the enhancing effect of 4-aminopyridine on the release of [H-3]noradrenaline depends on the entry of extracellular Ca2+ into the nerve terminals. That the magnitude of the effect of 4-aminopyridine differs per neurotransmitters and is particularly small or even absent for [H-3]D-aspartate supposedly reflects differences in the kinetics of Ca2+ entry into the terminals.