The relationship between the transport of glucose and cations across cell membranes in isolated tissues. IX. The role of cellular calcium in the activation of the glucose transport system in rat soleus muscle.

1. The role of cellular Ca2+ in the transport of glucose has been investigated by determining the time-course of tension development and the release of 45Ca and 3-0-[14C]methylglucose from preloaded rat soleus muscles. 2. Electrical stimulation, 2,4-dinitrophenol (0.05 mM) and hyperosmolarity (200 mM mannitol) were all found to induce a rapid rise in tension and the rate coefficient of 45Ca release, which coincided with an acceleration of 3-0-[14C]methylglucose efflux. 3. Caffeine (10 mM) or exposure to K+ -substituted buffer induced a rapid increase in tension and the release of 45Ca, but a much later stimulation of 3-0-methylglucose efflux. This delayed response may be related to the fact that both factors induce a pronounced suppression of the effect of various agents known to stimulate sugar transport.4. Following a washout period of 120 min at 0 degreesC, the return to 30 degrees C elicited a prompt transient rise in the rate coefficient for the release of 45Ca and 3-0-[14C]meth ylglucose to levels, respectively, 2.8 and 14.6 times the control levels measured at 30 degrees C. The magnitude of these peaks appeared to be a function of the duration of the exposure to 0 degrees C. Cooling also led to a stimulation of the uptake of 3-0-[14C]methylglucose, and phlorizin suppressed the rise. 5. It was not possible to detect any significant effect of insulin on basal tension or on the influx or efflux of 45Ca. However, in a hyperosmolar environment, insulin (10-100 munits/ml) induced a marked further rise in tension, indicating that the hormone can elicit a redistribution of cellular Ca2+. 6. It is concluded that a rise in the cytoplasmic concentration of free Ca2+ constitutes a part of the mechanism by which the glucose transport system is activated by a variety of stimuli, perhaps also insulin.