Ca(2+)-dependent heat production under basal and near-basal conditions in the mouse soleus muscle.
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.
Chinet
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A
Department of Physiology, University of Geneva, Switzerland.
Decrouy
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A
Even
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PC
D000818:Animals; D001481:Basal Metabolism; D001833:Body Temperature Regulation / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D003620:Dantrolene / Q000494:pharmacology; D003931:Diacetyl / Q000031:analogs & derivatives / Q000494:pharmacology; D004734:Energy Metabolism / Q000502:physiology*; D005033:Ethylmaleimide / Q000494:pharmacology; D006706:Homeostasis; D006873:Hydroquinones / Q000494:pharmacology; D051379:Mice; D009132:Muscles / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D002147:Calmodulin; D006873:Hydroquinones; C004717:diacetylmonoxime; C019359:2,5-di-tert-butylhydroquinone; D003620:Dantrolene; D003931:Diacetyl; D005033:Ethylmaleimide; D002118:Calcium