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

Norris SM, Bombardier E, Smith IC, Vigna C, Tupling AR. ATP consumption by sarcoplasmic reticulum Ca2+ pumps accounts for 50% of resting metabolic rate in mouse fast and slow twitch skeletal muscle. Am J Physiol Cell Physiol 298: C521-C529, 2010. First published December 16, 2009; doi: 10.1152/ajpcell. 00479.2009.-In this study, we aimed to directly quantify the relative contribution of Ca2+ cycling to resting metabolic rate in mouse fast-twitch (extensor digitorum longus, EDL) and slow-twitch (soleus) skeletal muscle. Resting oxygen consumption of isolated muscles ((V)over dot(O2), mu l.g wet wt(-1).s(-1)) measured polarographically at 30 degrees C was similar to 25% higher in soleus (0.61 +/-. 03) than in EDL (0.46 +/- .03). To quantify the specific contribution of Ca2+ cycling to resting metabolic rate, cyclopiazonic acid (CPA), a highly specific inhibitor of sarco(endo) plasmic reticulum Ca2+ ATPases (SERCAs), was added to the bath at different concentrations (1, 5, 10, and 15 mu M). There was a concentration-dependent effect of CPA on ((V)over dot(O2), with increasing CPA concentrations up to 10 mu M resulting in progressively greater reductions in muscle (V)over dot(O2). There were no differences between 10 and 15 mu M CPA, indicating that 10 mu M CPA induces maximal inhibition of SERCAs in isolated muscle preparations. Relative reduction in muscle (V)over dot(O2) in response to CPA was nearly identical in EDL (1 mu M, 10.6 +/- 3.0%; 5 mu M, 33.2 +/- 3.4%; 10 mu M, 49.2 +/- 2.9%; 15 mu M, 50.9 +/- 2.1%) and soleus (1 mu M, 11.2 +/- 1.5%; 5 mu M, 37.7 +/- 2.4%; 10 mu M, 50.0 +/- 1.3%; 15 mu M, 49.9 +/- 1.6%). The results indicate that ATP consumption by SERCAs is responsible for similar to 50% of resting metabolic rate in both mouse fast-and slow-twitch muscles at 30 degrees C. Thus SERCA pumps in skeletal muscle could represent an important control point for energy balance regulation and a potential target for metabolic alterations to oppose obesity.