In vitro System for Studying Presynaptically Acting Neurotoxins

摘要

This study examined whether a simple model system, the clonal cell line PC12, can be used to study certain presynaptically acting neurotoxins. The effect of these toxins on the growth, viability and differentiation of PC12 cells and on the transport and/or secretion of dopamine and acetylcholine by these cells has been investigated. PC12 is a clonal cell line of rat pheochromocytoma, a tumor of the adrenal medulla. The cells synthesize catecholamines (primary dopamine) and acetylcholine, store each in separate vesicles, and secrete them spontaneously; over and above this spontaneous secretion the cells also exhibit depolarization-evoked, Ca2+-dependent release of dopamine and acetylcholine. The evoked release of dopamine release is by exocytosis as it is in normal neurons. We have recently shown that acetylcholine release form PC12 is also by exocytosis. The following classes of neurotoxins have been studied: Tetanus toxin and botulinum toxin; Beta-bungarotoxin; and BayK8644, nitrendipine, CG528392 diltiazem and nisoldipine which are calcium channel blockers and antagonists. PC12 cells are remarkably resistant to the neurotoxins described above. Keywords: Nerve cells, Calcium channels. (aw)