title: Store-operated Ca(2+) entry (SOCE) contributes to normal skeletal muscle contractility in young but not in aged skeletal muscle.
abstract: Muscle atrophy alone is insufficient to explain the significant decline in contractile force of skeletal muscle during normal aging. One contributing factor to decreased contractile force in aging skeletal muscle could be compromised excitation-contraction (E-C) coupling, without sufficient available Ca(2+) to allow for repetitive muscle contractility, skeletal muscles naturally become weaker. Using biophysical approaches, we previously showed that store-operated Ca(2+) entry (SOCE) is compromised in aged skeletal muscle but not in young ones. While important, a missing component from previous studies is whether or not SOCE function correlates with contractile function during aging. Here we test the contribution of extracellular Ca(2+) to contractile function of skeletal muscle during aging. First, we demonstrate graded coupling between SR Ca(2+) release channel-mediated Ca(2+) release and activation of SOCE. Inhibition of SOCE produced significant reduction of contractile force in young skeletal muscle, particularly at high frequency stimulation, and such effects were completely absent in aged skeletal muscle. Our data indicate that SOCE contributes to the normal physiological contractile response of young healthy skeletal muscle and that defective extracellular Ca(2+) entry through SOCE contributes to the reduced contractile force characteristic of aged skeletal muscle.
authors.affiliation: Department of Physiology and Biophysics, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Thornton
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhao
authors.forename: Noah
authors.initials: N
authors.lastname: Weisleder
authors.forename: Leticia S
authors.initials: LS
authors.lastname: Brotto
authors.forename: Sylvain
authors.initials: S
authors.lastname: Bougoin
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Nosek
authors.forename: Michael
authors.initials: M
authors.lastname: Reid
authors.forename: Brian
authors.initials: B
authors.lastname: Hardin
authors.forename: Zui
authors.initials: Z
authors.lastname: Pan
authors.forename: Jianjie
authors.initials: J
authors.lastname: Ma
authors.forename: Jerome
authors.initials: J
authors.lastname: Parness
authors.forename: Marco
authors.initials: M
authors.lastname: Brotto
mesh_terms: D000375:Aging / Q000502:physiology*; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D004558:Electric Stimulation; D056966:Excitation Contraction Coupling / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D009133:Muscular Atrophy / Q000473:pathology / Q000503:physiopathology; D009281:Naphthalenes / Q000494:pharmacology; D009532:Nickel / Q000378:metabolism; D009543:Nifedipine / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011753:Pyrones / Q000494:pharmacology; D013830:Thiadiazoles / Q000494:pharmacology
chemical_list: C476308:4-methyl-4'-(3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl)-1,2,3-thiadiazole-5-carboxanilide; D000813:Anilides; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009281:Naphthalenes; D010726:Phosphodiesterase Inhibitors; D011753:Pyrones; D013830:Thiadiazoles; D002110:Caffeine; D009532:Nickel; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; D009543:Nifedipine; D002118:Calcium