title: Sarcolipin overexpression improves muscle energetics and reduces fatigue.
abstract: Sarcolipin (SLN) is a regulator of sarcoendoplasmic reticulum calcium ATPase in skeletal muscle. Recent studies using SLN-null mice have identified SLN as a key player in muscle thermogenesis and metabolism. In this study, we exploited a SLN overexpression (Sln(OE)) mouse model to determine whether increased SLN level affected muscle contractile properties, exercise capacity/fatigue, and metabolic rate in whole animals and isolated muscle. We found that Sln(OE) mice are more resistant to fatigue and can run significantly longer distances than wild-type (WT). Studies with isolated extensor digitorum longus (EDL) muscles showed that Sln(OE) EDL produced higher twitch force than WT. The force-frequency curves were not different between WT and Sln(OE) EDLs, but at lower frequencies the pyruvate-induced potentiation of force was significantly higher in Sln(OE) EDL. SLN overexpression did not alter the twitch and force-frequency curve in isolated soleus muscle. However, during a 10-min fatigue protocol, both EDL and soleus from Sln(OE) mice fatigued significantly less than WT muscles. Interestingly, Sln(OE) muscles showed higher carnitine palmitoyl transferase-1 protein expression, which could enhance fatty acid metabolism. In addition, lactate dehydrogenase expression was higher in Sln(OE) EDL, suggesting increased glycolytic capacity. We also found an increase in store-operated calcium entry (SOCE) in isolated flexor digitorum brevis fibers of Sln(OE) compared with WT mice. These data allow us to conclude that increased SLN expression improves skeletal muscle performance during prolonged muscle activity by increasing SOCE and muscle energetics.
authors.affiliation: Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio;
authors.forename: Danesh H
authors.initials: DH
authors.lastname: Sopariwala
authors.affiliation: Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio;
authors.forename: Meghna
authors.initials: M
authors.lastname: Pant
authors.affiliation: Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio;
authors.forename: Sana A
authors.initials: SA
authors.lastname: Shaikh
authors.affiliation: Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio;
authors.forename: Sanjeewa A
authors.initials: SA
authors.lastname: Goonasekera
authors.affiliation: Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio; Howard Hughes Medical Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Molkentin
authors.affiliation: Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio;
authors.forename: Noah
authors.initials: N
authors.lastname: Weisleder
authors.affiliation: Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio;
authors.forename: Jianjie
authors.initials: J
authors.lastname: Ma
authors.affiliation: Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio;
authors.forename: Zui
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio; Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio; mperiasamy@sanfordburnham.org.
authors.forename: Muthu
authors.initials: M
authors.lastname: Periasamy
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002155:Calsequestrin / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D017079:Exercise Tolerance; D008297:Male; D008810:Mice, Inbred C57BL; D018763:Muscle Fatigue; D009124:Muscle Proteins / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D009218:Myosins / Q000378:metabolism; D010805:Physical Conditioning, Animal; D011510:Proteolipids / Q000502:physiology*; D019289:Pyruvic Acid / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism
chemical_list: D002155:Calsequestrin; D009124:Muscle Proteins; D011510:Proteolipids; C077258:sarcolipin; D019289:Pyruvic Acid; D002334:Carnitine O-Palmitoyltransferase; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D009218:Myosins; D002118:Calcium
keywords: Ca2+ ATPase; muscle fatigue; muscle metabolism