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

Abstract

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

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

“…The first assumption is supported by the recent description, in this laboratory (Chinet et al 1992), of a substantial, steady-state Ca2+-dependent heat during subthreshold-for-contracture potassium depolarization in mouse soleus muscles whose resting tension was not increased by more than about 2 %. In favour of the second hypothesis, the finding that an antiserum raised against bumetanidebinding proteins strongly inhibits regulatory cell volume increase, as well as unidirectional Cl-influx, in Ehrlich ascites cells during a hyperosmotic stress (Dunham, Jessen & Hoffmann, 1990) can be considered a serious argument.…”

“…Once more, this energy dissipation is only indirectly related to co-transport, and if only because of its enormousness (25 megajoules per mole) it cannot be mistaken for the energy cost of co-transport. It is the increase of Ca2+ recirculation between sarcoplasmic reticulum and sarcoplasm that dissipates much energy (Chinet et al 1992), whereas co-transport stimulation only triggers and maintains this increase during a hyperosmotic stress. The rate at which Ca2+ recirculates is not known, but it could be calculated from the rate of Ca2+-dependent heat if the overall energetic efficiency of the Ca2+ transport process(es) and the free energy change of Ca2+ between sareoplasmic reticulum and sareoplasm were known (i.e., if the molar enthalpy change for the overall process of Ca2+ uptake by sareoplasmic reticulum was known).…”

“…Part of this increase is due to stimulation of sodium entry through the Na+-H+ exchange pathway (Chinet & Giovannini, 1989) and can be suppressed by high concentrations of amiloride. Neither contracture nor the increase of the rate of muscle energy dissipation related to Ca2+ recirculation between sarcoplasm and sarcoplasmic reticulum, which is sensitive to dantrolene sodium and will be called here Ca2+-dependent heat (Chinet, Decrouy & Even, 1992), can be modified by amiloride. Both are suppressed in the nominal absence of extracellular sodium (Nat = 0, lithium ion substitution) or under low Na+ (15 mM), however, and are sensitive to ouabain.…”

ATP consumption by sarcoplasmic reticulum Ca2+ pumps accounts for 50% of resting metabolic rate in mouse fast and slow twitch skeletal muscle

“…For example, another approach that has been employed to determine the relative contribution of SR Ca 2ϩ cycling to resting energy expenditure in skeletal muscle is to measure the decrease in energy expenditure following exposure of the muscle to chemicals that indirectly inhibit SERCAs by inhibiting Ca 2ϩ leakage from SR Ca 2ϩ release channels (CRCs). Using this approach with direct calorimetry, Chinet et al (12) found that ϳ12-24% of resting energy expenditure in mouse soleus is related to Ca 2ϩ cycling across the SR membrane. Similar experiments on mouse soleus and extensor digitorum longus (EDL) muscles showed that 18 -22% of resting energy expenditure in both muscles is related to SR Ca 2ϩ uptake (20).…”

“…Surprisingly, no study has used specific inhibitors of SERCAs to directly quantify the relative contribution of SR Ca 2ϩ pumping to resting metabolic rate in intact skeletal muscle. Chinet et al (12) attempted this approach but found it problematic to separate the effects of blocking SR Ca 2ϩ uptake from the resulting rise in [Ca 2ϩ ] f and development of contracture on muscle energy expenditure. To accurately quantify the contribution of Ca 2ϩ cycling to resting metabolic rate in skeletal muscle, SERCA activity must be inhibited directly in conjunction with myosin ATPase activity.…”