Ca(2+)‐dependent heat production under basal and near‐basal conditions in the mouse soleus muscle.

Abstract

1. The rate of energy expended for the clearance of sarcoplasmic Ca2+ by sarcoreticular Ca2+ uptake process(es), plus the concomitant metabolic reactions, was evaluated from measurements of resting heat production by mouse soleus muscle before and after indirect inhibition of Ca2+ uptake by sarcoplasmic reticulum (SR). 2. Direct inhibition of the Ca2+, Mg(2+)‐ATPase of SR membrane in intact muscle preparations exposed to the specific inhibitor 2,5‐di(tert‐butyl‐1,4‐benzohydroquinone (tBuBHQ) slowly increased the rate of heat production (E). Indirect inhibition of SR Ca2+ uptake was obtained by reducing sarcoplasmic Ca2+ concentration (Ca2+i) as a consequence of reducing Ca2+ release from the SR using dantrolene sodium. This promptly decreased E by 12%. Exposure of the preparations to an Mg(2+)‐enriched environment (high Mg2+) or to the chemical phosphatase 2,3‐butanedione monoxime (BDM), two other procedures aimed at decreasing SR Ca2+ release, also acutely decreased E, by 20 and 24%, respectively. 3. Subthreshold‐for‐contracture depolarization of the sarcolemma achieved by increasing extracellular K+ concentration to 11.8 mM induced a biphasic increase of E: an initial peak to 290% of basal E, followed by a plateau phase at 140% of basal E during which resting muscle tension was increased by less than 3%. Most, if not all, of the plateau‐phase metabolic response was quickly suppressed by dantrolene or high Mg2+ or BDM. Another means of increasing SR Ca2+ cycling was to partially remove the calmodulin‐dependent control of SR Ca2+ release using the calmodulin inhibitor W‐7. The progressive increase in E with 30 microM‐W‐7 was largely reduced by dantrolene or high Mg2+ or BDM. 4. In the presence of either dantrolene or BDM to prevent the effect of W‐7 on SR Ca2+ release, exposure of the muscle to W‐7 acutely suppressed about 3% of E. This and the above results confirm that the plasmalemmal, calmodulin‐dependent Ca(2+)‐ATPase, although a qualitatively essential part of the Ca2+i homeostatic system of the cell, can only be responsible for a very minor part of the energy expenditure devoted to the homeostasis of Ca2+i. Active Ca2+ uptake by SR which, at least in the submicromolar range of Ca2+i, is expected to be responsible for most of this Ca(2+)‐dependent energy expenditure, might dissipate up to 25‐40% of total metabolic energy in the intact mouse soleus under basal and near‐basal conditions. © 1992 The Physiological Society