Mechanisms of Action of Clostridial Neurotoxins on Dissociated Mouse Spinal Cord Neurons in Cell Culture
Annual rept. 1 Jan-31 Dec 1989
MARYLAND UNIV BALTIMORE
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Experiments with tetanus toxin in the dissociated spinal cord neuronal system have thus far revealed that the toxin binds to the neurons and after a dose-dependent latent period produces convulsant activity manifest by paroxysmal depolarizing events PDE, abrupt depolarizing shifts typically 5-20 mV of membrane potential associated with triggered action potentials lasting 200-2000mS. This convulsant period is produced by the reduction and ultimate block of synaptic inhibition by the toxin. Tetanus toxin has been demonstrated to block release of neurotransmitter at a presynaptic locus Bergey et al., 1983, 1987. After the convulsant period produced by the toxin, the frequency of the PDE is reduced and ultimately these events disappear. This parallels the apparent disappearance of all spontaneous postsynaptic potentials, excitatory as well as inhibitory. Tetanus toxin has been demonstrated by quantal analysis to block the presynaptic release at excitatory synapses Bergey et al, 1987. Therefore, while tetanus toxin has a preferential effect on inhibitory neurotransmission, all synaptic transmission appears to be blocked by the toxin.
- Medicine and Medical Research