Different effects of types A and B botulinum toxin on transmitter release at the rat neuromuscular junction.
Blockade of neuromuscular transmission was produced in the lower hind limb of the rat by local injection of either crystalline type A botulinum toxin or purified type B botulinum neurotoxin. At 1, 3, 5 and 7 days after injection, the extensor digitorum longus nerve-muscle preparation was excised and analyzed in vitro for alterations in spontaneous and nerve stimulus-evoked quantal transmitter release. Muscles receiving type A toxin were paralyzed up to and including 7 days after injection. Muscles treated with type B toxin, although completely paralyzed at 1 and 3 days, twitched in response to nerve stimulation at 5 and 7 days after injection. Both toxins induced a marked decrease in the frequency of miniature endplate potentials but type A did so to a greater extent. The remaining population of miniature endplate potentials contained a greater frequency of potentials with small or large amplitudes and prolonged rise times compared to normal muscle. These changes were more pronounced with type A toxin than with type B toxin. In the presence of alpha-dinitrophenol (1 mM), high frequency, fast-rising miniature endplate potentials of uniform size reappeared. High K+ (20 mM) was less effective in this respect. At 3 days after toxin injection nerve impulse evoked transmitter release was reduced more for type A treated muscles than for type B. However, 3,4-diaminopyridine, an agent which increases nerve-evoked transmitter release by increasing Ca2+ influx, was more effective in reversing the paralysis in type A than in type B-treated muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
D015761:4-Aminopyridine / Q000031:analogs & derivatives*; D000077770:Amifampridine; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D004140:Dinitrophenols / Q000494:pharmacology; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D008297:Male; D009045:Motor Endplate / Q000502:physiology; D009469:Neuromuscular Junction / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission / Q000187:drug effects
D000631:Aminopyridines; D004140:Dinitrophenols; D018377:Neurotransmitter Agents; D015761:4-Aminopyridine; D001905:Botulinum Toxins; D000077770:Amifampridine