title: ATP consumption by sarcoplasmic reticulum Ca2+ pumps accounts for 50% of resting metabolic rate in mouse fast and slow twitch skeletal muscle.
abstract: In this study, we aimed to directly quantify the relative contribution of Ca(2+) 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 (Vo(2), microl.g wet wt(-1).s(-1)) measured polarographically at 30 degrees C was approximately 25% higher in soleus (0.61 +/- .03) than in EDL (0.46 +/- .03). To quantify the specific contribution of Ca(2+) cycling to resting metabolic rate, cyclopiazonic acid (CPA), a highly specific inhibitor of sarco(endo)plasmic reticulum Ca(2+) ATPases (SERCAs), was added to the bath at different concentrations (1, 5, 10, and 15 microM). There was a concentration-dependent effect of CPA on Vo(2), with increasing CPA concentrations up to 10 microM resulting in progressively greater reductions in muscle Vo(2). There were no differences between 10 and 15 microM CPA, indicating that 10 microM CPA induces maximal inhibition of SERCAs in isolated muscle preparations. Relative reduction in muscle Vo(2) in response to CPA was nearly identical in EDL (1 microM, 10.6 +/- 3.0%; 5 microM, 33.2 +/- 3.4%; 10 microM, 49.2 +/- 2.9%; 15 microM, 50.9 +/- 2.1%) and soleus (1 microM, 11.2 +/- 1.5%; 5 microM, 37.7 +/- 2.4%; 10 microM, 50.0 +/- 1.3%; 15 microM, 49.9 +/- 1.6%). The results indicate that ATP consumption by SERCAs is responsible for approximately 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.
authors.affiliation: Dept. of Kinesiology, Univ. of Waterloo, Waterloo, ON, Canada.
authors.forename: Sarah Michelle
authors.initials: SM
authors.lastname: Norris
authors.forename: Eric
authors.initials: E
authors.lastname: Bombardier
authors.forename: Ian Curtis
authors.initials: IC
authors.lastname: Smith
authors.forename: Chris
authors.initials: C
authors.lastname: Vigna
authors.forename: Allan Russell
authors.initials: AR
authors.lastname: Tupling
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001481:Basal Metabolism / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000201:enzymology*; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects / Q000201:enzymology*; D024462:Myosin Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D010101:Oxygen Consumption; D011048:Polarography; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; C444880:N-benzyl-p-toluene sulfonamide; D013449:Sulfonamides; D014050:Toluene; D000255:Adenosine Triphosphate; D024462:Myosin Type II; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid