title: Action potential-evoked calcium release is impaired in single skeletal muscle fibers from heart failure patients.
abstract: BACKGROUND
  Exercise intolerance in chronic heart failure (HF) has been attributed to abnormalities of the skeletal muscles. Muscle function depends on intact excitation-contraction coupling (ECC), but ECC studies in HF models have been inconclusive, due to deficiencies in the animal models and tools used to measure calcium (Ca2+) release, mandating investigations in skeletal muscle from HF patients. The purpose of this study was to test the hypothesis that Ca2+ release is significantly impaired in the skeletal muscle of HF patients in whom exercise capacity is severely diminished compared to age-matched healthy volunteers.
  
  
  RESULTS
  Using state-of-the-art electrophysiological and optical techniques in single muscle fibers from biopsies of the locomotive vastus lateralis muscle, we measured the action potential (AP)-evoked Ca2+ release in 4 HF patients and 4 age-matched healthy controls. The mean peak Ca2+ release flux in fibers obtained from HF patients (10±1.2 µM/ms) was markedly (2.6-fold) and significantly (p<0.05) smaller than in fibers from healthy volunteers (28±3.3 µM/ms). This impairment in AP-evoked Ca2+ release was ubiquitous and was not explained by differences in the excitability mechanisms since single APs were indistinguishable between HF patients and healthy volunteers.
  
  
  CONCLUSIONS
  These findings prove the feasibility of performing electrophysiological experiments in single fibers from human skeletal muscle, and offer a new approach for investigations of myopathies due to HF and other diseases. Importantly, we have demonstrated that one step in the ECC process, AP-evoked Ca2+ release, is impaired in single muscle fibers in HF patients.
authors.affiliation: Department of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Marino
authors.initials: M
authors.lastname: DiFranco
authors.affiliation: Department of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Marbella
authors.initials: M
authors.lastname: Quiñonez
authors.affiliation: Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Perry
authors.initials: P
authors.lastname: Shieh
authors.affiliation: Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Gregg C
authors.initials: GC
authors.lastname: Fonarow
authors.affiliation: Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cruz
authors.affiliation: Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Mario C
authors.initials: MC
authors.lastname: Deng
authors.affiliation: Department of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Julio L
authors.initials: JL
authors.lastname: Vergara
authors.affiliation: Department of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Holly R
authors.initials: HR
authors.lastname: Middlekauff
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D005260:Female; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D002118:Calcium