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Several polypeptide neurotoxins affect presynaptic functions by interfering with chemical neurotransmission. This group of toxins includes botulinum toxin1, tetanus toxin2, β-bungarotoxin3and black widow spider toxin (BWSTx)4–6. While the effect of the first three toxins is mainly a rapid and severe block of neurotransmitter release, BWSTx affects transmission by a massive stimulation of mediator release4–6. Despite various hypotheses put forward to explain the action of BWSTx at the level of nerve terminals, there is still a considerable degree of uncertainty as to the cation dependence of venom action7–11. Study of the toxin mode of action at the biochemical level has been hampered by the complexity and cellular heterogeneity of the preparations used, neuromuscular junction10or synaptosomes6. PC12 cell line, derived from a rat phaeochromocytoma12, seems to be an excellent model in view of its property of synthesising and storing noradrenaline, dopamine and acetylcholine, and releasing them in depolarising conditions13. We have recently shown that highly purified BWSTx stimulates secretion from PC12 cells of previously taken up radioactive dopamine (DA) and noradrenaline (NA) (ref. 14 and manuscript in preparation). We report here that the earliest detectable event after toxin treatment of such cells is a massive increase of cytosolic calcium.

The chemical composition of liver plasma membrane was studied in Wistar rats aged between 3 and 24 months. Results obtained indicate a significant age-dependent positive correlation of both the protein:phospholipid and cholesterol:phospholipid ratios, whereas the protein:cholesterol ratio seems to remain unaffected. Phospholipid analysis of liver plasma membrane reveals that only the phosphatidylcholine content has a significant negative correlation with age; all other phospholipid species remain basically unchanged.