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

• Published in: Brain research 1995-07, Vol.686 (2), p.233-238
• Main Authors: Versteeg, Dirk H.G., Heemskerk, Frank M.J., Spierenburg, Henk A., de Graan, Pierre N.E., Schrama, Loes H.
• Format: Article
• Language: English
• Subjects: 4-Aminopyridine; 4-Aminopyridine - pharmacology; Animals; Biological and medical sciences; Brain - metabolism; Brain region; Ca 2; Calcium - metabolism; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Hippocampus - metabolism; In Vitro Techniques; Male; Neurotransmitter Agents - metabolism; Nitrendipine - pharmacology; Norepinephrine - metabolism; Rats; Rats, Wistar; Release of radiolabelled neurotransmitters; Slice; Synaptosome; Synaptosomes - metabolism; Tissue Distribution; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(95)00515-R

4-Aminopyridine increased the release of [ 3H]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 [ 3H]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 [ 3H]catecholamine from cortex, septum, periaqueductal gray and striatum slices. The effects of the compound on the release of [ 3H]5-hydroxytryptamine and [ 14C]acetylcholine were less pronounced. At this concentration 4-aminopyridine had no effect on the release of [ 3H]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 Ca 2+ in the superfusion medium. This was also the case for the effect on the release of [ 3H]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%. Cd 2+ completely abolished the effect of 4-aminopyridine on the release of [ 3H]noradrenaline. These results confirm that the enhancing effect of 4-aminopyridine on the release of [ 3H]noradrenaline depends on the entry of extracellular Ca 2+ into the nerve terminals. That the magnitude of the effect of 4-aminopyridine differs per neurotransmitters and is particularly small or even absent for [ 3H]d-aspartate supposedly reflects differences in the kinetics of Ca 2+ entry into the terminals.