Alterations of spontaneous and evoked release of acetylcholine during dithiobiuret-induced neuromuscular weakness.
Daily treatment of rats with 2,4-dithiobiuret (DTB, 1 mg/kg/day i.p.) produces a flaccid neuromuscular weakness first observed in the hindlimbs after 5 to 6 days of treatment. This condition is characterized by diminished contractile strength following single shock and tetanic stimulation of the motor nerve, but no effect on contractions evoked by direct muscle stimulation, indicating an apparent impairment of motor axon conduction, junctional transmission or both. The purpose of the present study was to investigate further the neuromuscular depression caused by DTB using conventional intracellular microelectrode recording techniques. All experiments were conducted using the extensor digitorum longus muscle isolated from male rats treated for 6 to 7 days with 1 mg/kg/day i.p. of DTB or with 0.9% NaCl (1 ml/kg/day) as control. End-plate potentials (EPPs) and miniature end-plate potentials (MEPPs) were recorded from single junctions of DTB-poisoned or NaCl-treated paired controls. Muscles were transected ("cut muscle") to prevent contraction after peroneal nerve stimulation. EPP amplitude was decreased at the time of observable muscle weakness in DTB-treated rats. Endplate resting membrane potential was not affected. Decreased EPP amplitude was associated with a decrease in mean quantal content. Quantal content was depressed to an equivalent extent in DTB-treated rats when stimulus frequency was increased from 0.5 to 2, 5, 25 and 50 Hz. However, as the stimulus frequency was increased, preparations from DTB-treated rats were characterized by failures of nerve impulses to elicit an EPP.(ABSTRACT TRUNCATED AT 250 WORDS)
Atchison
W D
WD
Department of Pharmacology and Toxicology, Michigan State University, East Lansing.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects; D008297:Male; D009045:Motor Endplate / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000378:metabolism; D010243:Paralysis / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains; D013890:Thiourea / Q000031:analogs & derivatives* / Q000633:toxicity
D013890:Thiourea; D000109:Acetylcholine; C007540:2,4-dithiobiuret