The myoneural effects of lithium chloride on the nerve-muscle preparations of rats. Role of adenosine triphosphate-sensitive potassium channels.
The potential effects of lithium chloride on the neuromuscular transmission and muscular contraction were studied using in vitro and in vivo nerve-muscle preparations of rats. Addition of lithium chloride to the fluid bathing the isolated rat diaphragm produced a concentration-dependent inhibition of diaphragmatic contractions elicited by either indirect or direct electrical stimulation. The threshold concentrations were 1 mmol l(-1)and 3 mmol l(-1), respectively. Similarly, the intravenous administration of lithium chloride as bolus injections, produced a dose-dependent progressive inhibition of the indirectly- and directly-induced gastrocnemius muscle contractions during the 2-h period of investigation. The indirectly-induced contractions were much more sensitive to the inhibitory effect of lithium chloride than directly-induced contractions. Also, lithium chloride was found to be capable of enhancing the paralysis of the indirectly stimulated rat diaphragm in vitro and gastrocnemius muscle in vivo induced by either pipecuronium or succinylcholine. The combination of lithium chloride and pipecuronium led to a synergistic inhibition of the neuromuscular transmission, while the combination of lithium chloride and succinylcholine led to additive inhibition. Pretreatment with lithium chloride at the threshold concentrations enhanced the inhibitory effects of verapamil on diaphragmatic contractions elicited either indirectly or directly. The inhibitory effects of verapamil on the indirectly- and directly-induced rat gastrocnemius muscle contractions were potentiated by lithium chloride administration to rats. Glibenclamide was found to be capable of inhibiting the relaxant effects of lithium chloride on the indirectly- and directly-elicited contractions of rat diaphragm in vitro and rat gastrocnemius muscle in vivo, in a concentration- and dose-dependent manner, respectively. Doubling the concentration of magnesium in the bathing fluid potentiated the inhibitory effects of the threshold concentrations of lithium chloride on the diaphragmatic contractions induced either indirectly or directly. Pretreatment with 4-aminopyridine or barium chloride inhibited the relaxant effects of lithium chloride on the indirectly- and directly-elicited diaphragmatic contractions. The inhibitory effects of diazoxide on the indirectly-evoked contractions of rat diaphragm in vitro and rat gastrocnemius muscle in vivo were potentiated by lithium chloride. Pretreatment with glibenclamide inhibited markedly the combined effects of lithium chloride and diazoxide on the contractions of the diaphragm and gastrocnemius muscles induced indirectly. Additionally, the intravenous administration of lithium chloride into rats as bolus injections produced a dose-dependent progressive increase in plasma potassium level and a dose-dependent progressive decrease in the intracellular levels of adenosine triphosphate in the sciatic nerve and gastrocnemius muscle. It is concluded that lithium chloride, via activation of adenosine triphosphate- sensitive potassium channels, acts presynaptically to inhibit the neuromuscular transmission and acts at the muscle membrane to inhibit the muscular contraction.
Abdel-Zaher
A O
AO
Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt.
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D018692:Antimanic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003964:Diaphragm / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007551:Isotonic Contraction / Q000187:drug effects; D054086:KATP Channels; D018021:Lithium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000294:innervation; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D010243:Paralysis / Q000139:chemically induced / Q000517:prevention & control; D015221:Potassium Channels / Q000187:drug effects*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology; D014882:Water-Electrolyte Balance / Q000187:drug effects
D018528:ATP-Binding Cassette Transporters; D018692:Antimanic Agents; D002121:Calcium Channel Blockers; D007004:Hypoglycemic Agents; D054086:KATP Channels; D003473:Neuromuscular Nondepolarizing Agents; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D000255:Adenosine Triphosphate; D014700:Verapamil; D018021:Lithium Chloride; D008274:Magnesium; D005905:Glyburide