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Open Access Publications from the University of California

Action potential-evoked calcium release is impaired in single skeletal muscle fibers from heart failure patients

  • Author(s): DiFranco, M
  • Quiñonez, M
  • Shieh, P
  • Fonarow, GC
  • Cruz, D
  • Deng, MC
  • Vergara, JL
  • Middlekauff, HR
  • et al.

© 2014 DiFranco et al. 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. Methods and Findings: 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.

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