The paralytic agent 2,4-dithiobiuret decreases open time of murine skeletal muscle acetylcholine receptor channels.
2,4-Dithiobiuret (DTB) causes a delayed-onset neuromuscular weakness when given chronically to rats. Mechanisms underlying this effect involve disruptions of acetylcholine (ACh) release and possibly effects on the ACh receptor channel complex. Previous experiments demonstrated a decrease in decay time constants for end-plate currents and miniature end-plate currents of muscles from rats exhibiting DTB-induced muscle weakness compared with those of controls. The purpose of the present study was to determine whether the alteration in rise and decay times for synaptic currents was due to direct effects of DTB on ACh receptor channels. Currents carried through single ACh-activated channels were recorded using patch voltage-clamp techniques in G8 mouse myotubes exposed to DTB in their growth medium and from intact hemidiaphragm preparations of rats treated with DTB by examining fluctuations in membrane noise during iontophoresis of agonist. Exposure of myotubes to DTB (1 or 10 microM) decreased the mean channel open time induced by suberyldicholine for short durations of exposure, whereas longer exposures (24-48 h) to DTB were required in order for decreased open times for ACh as an agonist to be observed. In the absence of DTB, closed times for single channels of G8 cells were described by a two-exponential fit reflecting intraburst and interburst closures. At 1 microM DTB, the duration of gaps within bursts and of gaps between bursts increased.(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; D002478:Cells, Cultured; D007473:Ion Channels / Q000187:drug effects*; D007478:Iontophoresis; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology; D010243:Paralysis / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000187:drug effects*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D007473:Ion Channels; D011950:Receptors, Cholinergic; D013890:Thiourea; C007540:2,4-dithiobiuret