title: Ca2+ Binding/Permeation via Calcium Channel, CaV1.1, Regulates the Intracellular Distribution of the Fatty Acid Transport Protein, CD36, and Fatty Acid Metabolism.
abstract: Ca(2+) permeation and/or binding to the skeletal muscle L-type Ca(2+) channel (CaV1.1) facilitates activation of Ca(2+)/calmodulin kinase type II (CaMKII) and Ca(2+) store refilling to reduce muscle fatigue and atrophy (Lee, C. S., Dagnino-Acosta, A., Yarotskyy, V., Hanna, A., Lyfenko, A., Knoblauch, M., Georgiou, D. K., Poché, R. A., Swank, M. W., Long, C., Ismailov, I. I., Lanner, J., Tran, T., Dong, K., Rodney, G. G., Dickinson, M. E., Beeton, C., Zhang, P., Dirksen, R. T., and Hamilton, S. L. (2015) Skelet. Muscle 5, 4). Mice with a mutation (E1014K) in the Cacna1s (α1 subunit of CaV1.1) gene that abolishes Ca(2+) binding within the CaV1.1 pore gain more body weight and fat on a chow diet than control mice, without changes in food intake or activity, suggesting that CaV1.1-mediated CaMKII activation impacts muscle energy expenditure. We delineate a pathway (Cav1.1→ CaMKII→ NOS) in normal skeletal muscle that regulates the intracellular distribution of the fatty acid transport protein, CD36, altering fatty acid metabolism. The consequences of blocking this pathway are decreased mitochondrial β-oxidation and decreased energy expenditure. This study delineates a previously uncharacterized CaV1.1-mediated pathway that regulates energy utilization in skeletal muscle.
authors.affiliation: From the Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030 and.
authors.forename: Dimitra K
authors.initials: DK
authors.lastname: Georgiou
authors.affiliation: From the Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030 and.
authors.forename: Adan
authors.initials: A
authors.lastname: Dagnino-Acosta
authors.affiliation: From the Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030 and.
authors.forename: Chang Seok
authors.initials: CS
authors.lastname: Lee
authors.affiliation: From the Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030 and.
authors.forename: Deric M
authors.initials: DM
authors.lastname: Griffin
authors.affiliation: From the Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030 and.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: From the Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030 and.
authors.forename: William R
authors.initials: WR
authors.lastname: Lagor
authors.affiliation: From the Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030 and.
authors.forename: Robia G
authors.initials: RG
authors.lastname: Pautler
authors.affiliation: the Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York 14642.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Dirksen
authors.affiliation: From the Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030 and susanh@bcm.edu.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Hamilton
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008931:Mitochondria, Muscle / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: C529218:CACNA1S protein, mouse; D018955:CD36 Antigens; D020746:Calcium Channels, L-Type; D005227:Fatty Acids; D019001:Nitric Oxide Synthase; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium
keywords: CD36; Ca2+ channel; Ca2+/calmodulin-dependent protein kinase II (CaMKII); CaM kinase II; CaV1.1; S-nitrosylation; calcium channel; metabolic rate; metabolism; mitochondria; mitochondrial beta oxidation; nitric-oxide synthase; skeletal muscle