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.