Effects of carbonyl cyanide m-chlorophenylhydrazone on quantal transmitter release and ultrastructure of frog motor nerve terminals.
The quantal acetylcholine release and the ultrastructural effects of the metabolic inhibitor carbonyl cyanide m-chlorophenylhydrazone have been examined at frog neuromuscular junctions. Carbonyl cyanide m-chlorophenylhydrazone (2 microM) caused a temperature-dependent block of evoked quantal transmitter release accompanied by an increase in the rate of spontaneous quantal release. The carbonyl cyanide m-chlorophenylhydrazone-induced increase in miniature endplate potential frequency was neither antagonized nor prevented by tetrodotoxin. It also occurred in a Ca2+-free medium and after replacement of Ca2+ by Sr2+, indicating that it does not depend upon a Na+ or Ca2+ influx from the external medium but may act by releasing Ca2+ from intraterminal stores. Spontaneous quantal transmitter release was exhausted irreversibly within 4 h of carbonyl cyanide m-chlorophenylhydrazone (2 microM) action, during which time an average of 4.7 x 10(5) acetylcholine quanta were released per junction. The morphologic analysis revealed a significant temperature and time-dependent reduction in the number of synaptic vesicles with swelling and dispersion of mitochondria within the motor nerve terminals. Changes in synaptic vesicle number appear to be directly related to the intensity of transmitter release. The good correlation observed between the number of quanta secreted and the number of vesicles lost by nerve terminals in the absence of vesicle recycling provides an estimate of the initial store of transmitter quanta.
Molgo
J
J
Laboratoire de Neurobiologie Cellulaire et Moléculaire du CNRS, Gif sur Yvette, France.
Pecot-Dechavassine
M
M
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008854:Microscopy, Electron; D009045:Motor Endplate / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology*; D011893:Rana esculenta; D009435:Synaptic Transmission / Q000187:drug effects*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology
D009570:Nitriles; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000109:Acetylcholine