Effect of chronic lithium chloride on membrane adenosine triphosphatases in certain postural muscles of rats.

Lithium has been extensively used as an antidepressant in the treatment of manic depressive disorders requiring chronic administration. Here, we report a study of the effect of long-term lithium treatment on the activities of membrane adenosine triphosphatases (ATPases) in certain postural muscles of rat. Specifically, Ca(2+)-ATPase, Na+,K(+)-ATPase and Mg(2+)-ATPase activities were measured in the soleus, extensor digitorum longus and plantaris muscles following 6 weeks of treatment with LiCl. Increases were observed in the Na+,K(+)-ATPase activity whereas the Mg(2+)-ATPase activity decreased with prolonged LiCl treatment. The most pronounced effect was a highly significant (P < 0.001) increase in the mitochondrial Ca(2+)-ATPase and Na+,K(+)-ATPase activity to almost 50-100% above the control. The increases in the mitochondrial Ca(2+)-ATPase activity of extensor digitorum longus and plantaris were 70% and 100%, respectively. The corresponding increases in the Na+,K(+)-ATPase activity were 127%, 99% and 87% for soleus, extensor digitorum longus and plantaris, respectively. Irrespective of the differences in the fiber pattern and physiological function, all three muscles responded in a similar way to Li+. The changes in the membrane ATPases reflect a deranged ATP turnover, thus affecting the overall energy state of the animal. Based on these results, we hypothesize that Li+ produces its effects by interfering with cation transport processes. Since Li+ affects the neural excitability of the cell it is suggested that the stimulation of the ATPases may be important in the psychotropic properties of the ion.