Voltage clamp analysis reveals multiple populations of quanta released at neuromuscular junctions of rats treated with 2,4-dithiobiuret.
Rats treated with small daily doses of 2,4-dithiobiuret (DTB) develop a delayed onset neuromuscular weakness after 4-6 days of treatment. Analysis of quantal release using nerve-muscle preparations taken from rats exhibiting neuromuscular weakness demonstrated a decrease in quantal content of evoked end-plate potentials (EPP), a decrease in the frequency of spontaneously occurring miniature end-plate potentials (MEPP) and a prolongation of rise and decay times for MEPPs. This latter effect is also observed in muscles taken from rats after one large dose of DTB; in which no weakness is observed. Moreover, an increase in the incidence of abnormally large amplitude MEPPs has also been observed after both acute and chronic treatment of rats with DTB. The purpose of the present study was to determine whether the observed prolongation of rise and decay times for the spontaneous synaptic events observed after exposure to DTB can be attributed to a generalized slowing of all synaptic events or whether DTB causes an increase in a distinct population of abnormal synaptic events. End-plate currents and miniature end-plate currents (MEPC) were recorded, using two microelectrode voltage clamp, from hemidiaphragm preparations of rats after acute administration of 25 mg/kg and chronic treatment with 1 mg/kg/day (7-8 days) DTB. Mean MEPC amplitude calculated for all MEPCs was unaffected by DTB treatment; however there was an increase in the incidence of giant MEPCs after both acute and chronic treatments.(ABSTRACT TRUNCATED AT 250 WORDS)
Spitsbergen
J M
JM
Department of Pharmacology and Toxicology, Michigan State University, East Lansing.
Atchison
W D
WD
D000818:Animals; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009045:Motor Endplate / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D013890:Thiourea; C007540:2,4-dithiobiuret