SUMMARY1. The rate of energy expended for the clearance of sarcoplasmic Ca2+ by sarcoreticular Ca2+ uptake processess, 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+, Mg2+-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+) 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 Mg2+-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 pm-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 Ca2+-ATPase, although a qualitatively essential part of the Ca2+ homeostatic system of the cell, can only be responsible for a very minor part of the energy expenditure devoted to the homeostasis of Ca 2+. Active Ca2+ uptake by SR which, at least in the submicromolar range of Cai , is expected to be responsible for most of this Ca2+-dependent energy expenditure, might dissipate up to 25-40% of total metabolic energy in the intact mouse soleus under basal and near-basal conditions.
MS 9801 22PHY 455