Cooperative action of the light chain of tetanus toxin and the heavy chain of botulinum toxin type A on the transmitter release of mammalian motor endplates.
Purified heavy chain of botulinum toxin type A and light chain of tetanus toxin were combined to form a chimeric toxin. It was active on the mouse phrenic nerve-hemidiaphragm with a potency 6 times higher than that of native tetanus toxin. Electrophysiological data from poisoned neuromuscular junctions revealed that the pattern of nerve-evoked and spontaneous transmitter release was equivalent to that seen with tetanus toxin i.e. asynchronous release, and did not resemble that after botulinum toxin type A poisoning. We conclude that the light chain of tetanus toxin alone is responsible for the characteristic effects on spontaneous and nerve-evoked transmitter release of the native toxin and that these properties can be introduced into a new, more potent complex with the heavy chain of botulinum toxin A.
Rudolf-Buchheim-Institut für Pharmakologie der Justus-Liebig-Universität, Giessen, F.R.G.
U
U
Weller
M E
ME
Dauzenroth
M
M
Gansel
F
F
Dreyer
D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D004558:Electric Stimulation; D004594:Electrophysiology; D066298:In Vitro Techniques; D051379:Mice; D009045:Motor Endplate / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010791:Phrenic Nerve / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D013744:Tetanus Toxin / Q000494:pharmacology*
D018377:Neurotransmitter Agents; D013744:Tetanus Toxin; D001905:Botulinum Toxins