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

Abstract

We have investigated the relation between the stimulation of sugar transport by Li + and Li +-induced changes in cellular Ca 2+ distribution. The fluxes of 3-O-[ 14 C] methyl- d-glucose and 45Ca were measured in hemidiaphragm, soleus, and cardiac muscles of the rat, and cellular levels of Ca 2+, Na + and K + were determined. Li + increased in parallel the fluxes of 3-O-[ 14 C] ethyl- d-glucose and 45Ca in rat hemidiaphragm and soleus muscles. Sugar transport and Ca 2+ efflux were also stimulated by Li + in Ca 2+-free medium, suggesting that in addition to increasing sarcolemmal Ca 2+ influx, Li + may also cause the release of Ca 2+ from intracellular storage sites, presumably the mitochondria. Mitochondria were isolated from preparations of rat ventricular muscle exposed to Li +, and their Ca 2+ content was determined. In rat cardiac muscle, Li + stimulation of sugar transport was associated with decreased mitochondrial Ca 2+ levels (indicating mitochondrial Ca 2+ release) only under conditions of deteriorating mitochondrial function. Thus, Li +-induced changes in cellular Ca 2+ distribution, which would increase cytosolic Ca 2+ levels, were associated with stimulation of sugar transport. These observation support the hypothesis that the increased availability of cytosolic Ca 2+ regulates the activity of the sugar transport system in muscle.