Transmitter release in tetanus and botulinum A toxin-poisoned mammalian motor endplates and its dependence on nerve stimulation and temperature

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Abstract
The effects of tetanus toxin (TeTx) and botulinum A toxin (BoTx) on spontaneous and nerve-evoked transmitter release have been compared in mouse hemidiaphragms poisoned in vitro. At 37°C endplates poisoned with either of these agents were characterized by (1) a decrease of miniature endplate potential (m.e.p.p.)-frequency to less than 30/min for TeTx and 3/min for BoTx, (2) reduced mean m.e.p.p.-amplitude and (3) 100% failure to show endplate potentials (e.p.p.s) in response to single nerve stimuli. In addition (4) tetanic nerve stimulation and/or reduction of temperature to about 20°C caused a remarkable increase in the nerveevoked transmitter release, but did not affect the low frequency of spontaneous m.e.p.p.s. However, several important differences exist between the effects of both toxins. (1) At room temperature even single nerve stimuli could elicit e.p.p.s in BoTx-muscles the failure rate being about 80%. For TeTx the failure was 100%. However, if the nerve was stimulated with higher frequencies (>5Hz), the probability of quantal release increased, the delay for release from the onset of stimulation being several seconds and similar to that observed at 37°C. (2) TeTx distorted the synchronous release of quanta increasing the distribution of their synaptic delays. BoTx did not influence the time course of the phasic secretion process in response to nerve action potentials. (3) TeTx preferentially blocked the release of spontaneous m.e.p.p.s of large amplitude without affecting the frequency of the small amplitude ones, while BoTx inhibited both the small and large amplitude m.e.p.p.s. The distribution of the amplitudes of the nerve-evoked m.e.p.p.s were similar to those of spontaneous m.e.p.p.s before the blockade with the toxins. We conclude that TeTx and BoTx act at different stages in the chain of events that result in spontaneous and in nerveevoked transmitter release at motor endplates.