The role of calcium in stimulation of sugar transport in muscle by lithium.

We have investigated the relation between the stimulation of sugar transport by Li+ and Li+-induced changes in cellular Ca2+ distribution. The fluxes of 3-O-[14C]methyl-D-glucose and 45Ca were measured in hemidiaphragm, soleus, and cardiac muscles of the rat, and cellular levels of Ca2+, Na+ and K+ were determined. Li+ increased in parallel the fluxes of 3-O-[14C]methyl-D-glucose and 45Ca in rat hemidiaphragm and soleus muscles. Sugar transport and Ca2+ efflux were also stimulated by Li+ in Ca2+-free medium, suggesting that in addition to increasing sarcolemmal Ca2+ influx, Li+ may also cause the release of Ca2+ from intracellular storage sites, presumably the mitochondria. Mitochondria were isolated from preparations of rat ventricular muscle exposed to Li+, and their Ca2+ content was determined. In rat cardiac muscle, Li+ stimulation of sugar transport was associated with decreased mitochondrial Ca2+ levels (indicating mitochondrial Ca2+ release) only under conditions of deteriorating mitochondrial function. Thus, Li+-induced changes in cellular Ca2+ distribution, which would increase cytosolic Ca2+ levels, were associated with stimulation of sugar transport. These observations support the hypothesis that the increased availability of cytosolic Ca2+ regulates the activity of the sugar transport system in muscle.