Neuromuscular actions of sodium selenite on chick biventer cervicis nerve-muscle preparation.
Sodium selenite was found to be toxic to chicks, with an LD50 of 8.5 micrograms/g, which was increased to 16.3 micrograms/g by NaCN. The major symptoms of chicks, treated with selenite, were sedation and then dyspnea and paralysis. The cause of death by selenite was apparently due to the respiratory failure. The possible mechanism of toxicity was explored in the isolated chick biventer cervicis nerve-muscle preparation. Selenite initially increased the amplitude of the twitch, reversed the suppression of the twitch caused by d-tubocurarine, Mg2+, Cd2+ or Mn2+ and significantly increased the quantal content and amplitude of endplate potentials. Subsequently, selenite depressed the amplitude of the twitch, blocked the axonal conduction and inhibited excitatory postsynaptic potentials. Both NH4+ and K+ enhanced the action of selenite in depressing the twitches. In addition, selenite induced a sustained contracture of the muscle, which was partially inhibited by removal of external Ca2+ and markedly blocked by EGTA. Entry of Ca2+ and release of the internal Ca2+ were considered to be responsible for inducing contracture by selenite. Pretreatment with trypsin, glutathione (GSH) and cyanide profoundly inhibited the effects of selenite, indicating that the site of action of selenite was on the outer membrane and the binding of selenite to the sulfhydryl groups of membrane proteins was proposed to be an essential step for selenite-induced contracture and neuromuscular action. These findings suggest that neuromuscular blockade and tetanic spasm, produced by selenite in chicks, may play a role in causing respiratory failure in vivo.
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, R.O.C.
S Y
SY
Lin-Shiau
S H
SH
Liu
W M
WM
Fu
D000818:Animals; D001370:Axonal Transport / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D002645:Chickens; D003486:Cyanides / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D066298:In Vitro Techniques; D008839:Microelectrodes; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects*; D010791:Phrenic Nerve / Q000187:drug effects; D012132:Respiratory Muscles / Q000187:drug effects / Q000294:innervation; D012643:Selenium / Q000494:pharmacology*; D018038:Sodium Selenite; D009435:Synaptic Transmission / Q000187:drug effects; D014357:Trypsin / Q000494:pharmacology
D003486:Cyanides; D009467:Neuromuscular Depolarizing Agents; D002110:Caffeine; D014357:Trypsin; D005978:Glutathione; D012643:Selenium; D018038:Sodium Selenite