Diphenylhydantoin-induced block of the rat phrenic nerve-diaphragm preparation pretreated with p-hydroxymercuribenzoate.
Pretreatment of the rat phrenic nerve-diaphragm preparation with the sulfhydryl-(SH) blocking agent p-hydroxymercuribenzoate (pOHMB) increased the blocking efficiency of the antiepileptic drug diphenylhydantoin (DPH) during indirect stimulation. Another SH-blocking agent, N-ethyl-maleimide (NEM) did not potentiate the block, but SH-group protection with dithiothreitol (DTT) abolished the effect of pOHMB. SH-binding was thus necessary but not sufficient for enhancement of DPH-block. High Ca2+-concentration potentiated the block. Well-maintained response of the isolated phrenic nerve, and of the diaphragm during direct stimulation, located the block at the neuromuscular junction. Microelectrode records in preparations which were curarized, cut or Mg2+ paralyzed to abolish action potential activity, disclosed an abrupt cessation of end-plate potentials (EPPs) by DPH, and pOHMB pretreatment reduced the time period to abrupt EPP fallout in the curarized preparation, suggesting depressed nerve terminal excitability as the cause of the block and its potentiation. Observation of miniature EPPs beyond the time of EPP cessation excluded a postsynaptic block. The pOHMB-treated preparation is suggested as a model for testing antiepileptic drugs.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003964:Diaphragm / Q000502:physiology; D004357:Drug Synergism; D005033:Ethylmaleimide / Q000494:pharmacology; D005260:Female; D006902:Hydroxymercuribenzoates / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D010672:Phenytoin / Q000494:pharmacology*; D010791:Phrenic Nerve / Q000502:physiology; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects
D006902:Hydroxymercuribenzoates; D010672:Phenytoin; D008274:Magnesium; D005033:Ethylmaleimide; D002118:Calcium