On the mechanism of spontaneous recovery of neuromuscular transmission after acetylcholinesterase inhibition in the rat neuromuscular junction.
Neuromuscular transmission shows a significant degree of spontaneous recovery after being impeded by acetylcholinesterase inhibition. Part of this recovery can be ascribed to de novo synthesis of acetylcholinesterase but another part is independent of enzyme activity. To unravel the mechanism underlying this synaptic adaptation to acetylcholinesterase inhibition we have compared a number of electrophysiological parameters in diaphragms taken from animals that were sacrificed within 15 min after a 2 x LD50 dose of the acetylcholinesterase inhibitor diisopropylfluorophosphate and from similarly treated animals killed after being kept alive for 3 h under artificial respiration. We found no differences in the quantal content. There was a significantly smaller degree of endplate potential rundown at tetanic stimulation and the miniature endplate potential amplitude was smaller in the 3-h adapted animals. In addition, the desensitization induced by carbachol appeared to be less in this group. It is likely that these synaptic changes, demonstrating the plasticity of the neuromuscular synapse, are involved in the spontaneous recovery of neuromuscular transmission after acetylcholinesterase inhibition.
Melchers
B P
BP
Medical Biological Laboratory T.N.O., Rijswijk, The Netherlands.
Van der Laaken
A L
AL
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003964:Diaphragm / Q000201:enzymology / Q000502:physiology; D004558:Electric Stimulation; D004594:Electrophysiology; D066298:In Vitro Techniques; D007531:Isoflurophate / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009045:Motor Endplate / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012132:Respiratory Muscles / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000201:enzymology; D009435:Synaptic Transmission / Q000187:drug effects*
D002800:Cholinesterase Inhibitors; D007531:Isoflurophate; D002217:Carbachol