Transmitter release in botulinum-poisoned muscles.
Examination of miniature end-plate potentials (m.e.p.ps) in rat skeletal muscle poisoned in vivo by botulinum toxin type A reveals the presence of two populations of potentials. One population which corresponds to m.e.p.ps in unpoisoned muscles and to quantal end-plate potentials. The frequency of these m.e.p.ps is greatly reduced by botulinum toxin. The second population of m.e.p.ps has quite different characteristics. These m.e.p.ps have a more variable, but generally much larger amplitude, and their time to peak is longer than normal m.e.p.ps. The frequency of these m.e.p.ps increases during poisoning and reaches 0.3-1 Hz after 10-14 days. In addition to the variability in amplitude and time-to-peak these m.e.p.ps differ from those at unpoisoned junctions by being unaffected by procedures which alter extra- or intracellular Ca2+ concentrations. The appearance of this Ca2+-insensitive spontaneous quantal secretion of acetylcholine is apparently not a direct effect of the toxin but secondary to blockade of impulse transmission since it also appears at unpoisoned end-plates when transmission is impaired for other reasons. Procedures which increase the intracellular Ca2+ concentration in nerve terminals restore transmitter release from botulinum toxin poisoned nerves. Furthermore, the block caused by the toxin is very temperature-dependent, a reduction in temperature relieving the block. Since presynaptic Ca2+ currents are unaltered by the toxin it is proposed that the block of transmission is due to a reduction in the calcium content of the nerve terminal to a level where the amount of Ca2+, which normally enters, is insufficient to activate transmitter release.
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology / Q000506:poisoning*; D002118:Calcium / Q000378:metabolism; D004594:Electrophysiology; D007473:Ion Channels / Q000187:drug effects; D009045:Motor Endplate / Q000503:physiopathology; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D013696:Temperature
D007473:Ion Channels; D009498:Neurotoxins; D018377:Neurotransmitter Agents; D001905:Botulinum Toxins; D000109:Acetylcholine; D002118:Calcium