Mechanisms of Action of Clostridial Neurotoxins on Dissociated Mouse Spinal Cord Neurons in Cell Culture.

摘要

The research conducted during this period continued the previous studies of structure function relationships of tetanus toxin with monoclonal antibodies studied in the previous years. Tetanus toxin is one of the most toxic substances known. After being bound to nerve terminals peripherally it moves by retrograde axonal transport to the ventral spinal cord (Price et al., 1975). The toxin then moves transsynaptically to the presynaptic terminals where it acts to block presynaptic release of neurotransmitter (Schwab et al., 1976, Bergley et al., 1987). Despite the extreme potency of tetanus toxin, little is known about its cellular locus of action. It has been speculated that, following binding, tetanus toxin moves intracellularly to an unknown site to ultimately block presynaptic neurotransmitter release (Schmitt et al., 1981, Critchley et al., 1985). Some recent studies with intracellular injections of tetanus toxin into adrenal chromaffin cells supports this (Penner et al., 1986). The dissociated mouse spinal cord culture system has allowed characterization of the actions of tetanus toxin. After a dose-dependent latent period the toxin produces convulsant activity due to the preferential reduction in inhibitory synaptic transmission.