Ca(2+)-dependent heat production by rat skeletal muscle in hypertonic media depends on Na(+)-Cl- co-transport stimulation.

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Abstract
1. The rate of energy dissipation (E) in isolated, superfused soleus muscles from young rats was continuously measured under normosmotic and 100-mosM hyperosmotic conditions. The substantial increase of E with respect to basal level in hyperosmolarity (excess E), which is entirely dependent on the presence of extracellular sodium, was largely prevented or inhibited by bumetanide, a potent inhibitor of Na(+)-Cl- co-transport system, or by the removal of chloride from the superfusate (isethionate substitution). Bumetanide or the removal of chloride also acutely decreased basal E, by about 7%. 2. Bumetanide almost entirely suppressed the major, Ca(2+)-dependent part of excess E in hyperosmolarity, as well as the concomitant increase of 45Ca2+ efflux and small increase in resting muscle tension; in contrast, the part of excess E associated with stimulation of Na(+)-H+ exchange in hyperosmolarity was left unmodified. 3. Reduction of 22Na+ influx by bumetanide was more marked in hyperosmolarity than under control conditions, although stimulation of total 22Na+ influx by a 100-mosM stress was not statistically significant. Inhibition of Ca2+ release into the sarcoplasm using dantrolene sodium did not prevent the stimulation of bumetanide-sensitive 22Na+ influx, but rather increased it about fourfold. 4. It is concluded that the largest part of excess E in hyperosmolarity, which is Ca(2+)-dependent energy expenditure, is suppressed when steady-state stimulation of a Na(+)-Cl- co-transport system is inhibited either directly by bumetanide or the removal of extracellular chloride, or indirectly by the blocking of active Na(+)-K+ transport. How the stimulation of Na(+)-Cl- co-transport, by as little as 1 nmol s-1 (g wet muscle weight)-1 during a 100-mosM stress, enhances Ca(2+)-dependent heat by as much as 2.5 mW (g wet muscle weight)-1 remains to be clarified.