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

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 (Vo2, μl·g wet wt−1·s−1) measured polarographically at 30°C was ∼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 μM). There was a concentration-dependent effect of CPA on Vo2, with increasing CPA concentrations up to 10 μM resulting in progressively greater reductions in muscle Vo2. There were no differences between 10 and 15 μM CPA, indicating that 10 μM CPA induces maximal inhibition of SERCAs in isolated muscle preparations. Relative reduction in muscle Vo2 in response to CPA was ne...