Differential effects of various secretagogues on quantal transmitter release from mouse motor nerve terminals treated with botulinum A and tetanus toxin.
Electrophysiological and electron microscopic techniques were used to investigate the actions of potassium depolarization, black widow venom (BWSV), Ca2+-ionophore A 23187 and hyperosmotic solution on mouse hemidiaphragms poisoned in vitro with botulinum A toxin (BoTx) and tetanus toxin (TeTx). These neurotoxins reduced the frequency of miniature endplate potentials (m.e.p.ps) from 5/s of the control to 2/min and 21/min, respectively. High potassium (25 mmol/l) increased the m.e.p.p.-frequency at BoTx- and TeTx-poisoned endplates to 30/min and 50/s, respectively. The ultrastructure of endplates showed no obvious changes. BWSV (0.04 glands/ml) was just as effective in promoting transmitter release from BoTx-treated endplates as in control preparations. Electron micrographs revealed depletion of vesicles as well as swollen and disrupted mitochondria. When preparations were pretreated with TeTx, BWSV only moderately increased transmitter release and no alterations of the ultrastructure could be observed. At TeTx- or BoTx-poisoned endplates Ca2+-ionophore A 23187 usually produced an extreme reduction of m.e.p.p.-frequency (0.005/s), sometimes preceded by a short burst-like release. The ultrastructure of these endplates was not obviously affected. Application of hyperosmotic solution to BoTx- or TeTx-poisoned preparations further reduced the already low m.e.p.p.-frequency. These results further demonstrate that TeTx and BoTx act at different sites in the transmitter releasing process.
D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D006982:Hypertonic Solutions / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009467:Neuromuscular Depolarizing Agents; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D013111:Spider Venoms / Q000494:pharmacology; D013744:Tetanus Toxin / Q000494:pharmacology*
D006982:Hypertonic Solutions; D009467:Neuromuscular Depolarizing Agents; D018377:Neurotransmitter Agents; D013111:Spider Venoms; D013744:Tetanus Toxin; D000001:Calcimycin; D001905:Botulinum Toxins; D011188:Potassium; C038599:black widow spider venom