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Excitation-calcium release uncoupling in aged single human skeletal muscle fibers

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Abstract

The biological mechanisms underlying decline in muscle power and fatigue with age are not completely understood. The contribution of alterations in the excitation-calcium release coupling in single muscle fibers was explored in this work. Single muscle fibers were voltage-clamped using the double Vaseline gap technique. The samples were obtained by needle biopsy of the vastus lateralis (quadriceps) from 9 young (25–35 years; 25.9 ± 9.1; 5 female and 4 male) and 11 old subjects (65–75 years; 70.5 ± 2.3; 6 f, 5 m). Data were obtained from 36 and 39 fibers from young and old subjects, respectively. Subjects included in this study had similar physical activity. Denervated and slow-twitch muscle fibers were excluded from this study. A significant reduction of maximum charge movement (Qmax) and DHP-sensitive Ca current were recorded in muscle fibers from the 65–75 group. Qmax values were 7.6 ± 0.9 and 3.2 ± 0.3 nC/μF for young and old muscle fibers, respectively (P < 0.01). No evidences of charge inactivation or interconversion (charge 1 to charge 2) were found. The peak Ca current was (−)4.7 ± 0.08 and (−)2.15 ± 0.11 μA/μF for young and old fibers, respectively (P < 0.01). The peak calcium transient studied with mag-fura-2 (400 μm) was 6.3 ± 0.4 μm and 4.2 ± 0.3 μm for young and old muscle fibers, respectively. Caffeine (0.5 mm) induced potentiation of the peak calcium transient in both groups. The decrease in the voltage-/ Ca-dependent Ca release ratio in old fibers (0.18 ± 0.02) compared to young fibers (0.47 ± 0.03) (P < 0.01), was recorded in the absence of sarcoplasmic reticulum calcium depletion. These data support a significant reduction of the amount of Ca available for triggering mechanical responses in aged skeletal muscle and, the reduction of Ca release is due to DHPR-ryanodine receptor uncoupling in fast-twitch fibers. These alterations can account, at least partially for the skeletal muscle function impairment associated with aging.

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Authors and Affiliations

  1. Departments of Physiology and Pharmacology, and Internal Medicine (Gerontology), Bowman Gray School of Medicine, Wake Forest University, Medical Center Boulevard, 27157, Winston-Salem, NC

    O. Delbono

  2. Department of Internal Medicine (Rheumatology), Bowman Gray School of Medicine, Wake Forest University, Medical Center Boulevard, 27157, Winston-Salem, NC

    K. S. O'Rourke

  3. Departments of Internal Medicine (Gerontology) and Public Health Sciences, Bowman Gray School of Medicine, Wake Forest University, Medical Center Boulevard, 27157, Winston-Salem, NC

    W. H. Ettinger

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  1. O. Delbono
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  2. K. S. O'Rourke
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  3. W. H. Ettinger
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This work was supported by Grant-in-Aid from the American Heart Association (National) and Muscular Dystrophy Association, and National Institutes of Health (2-P60AG18484-06)

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Delbono, O., O'Rourke, K.S. & Ettinger, W.H. Excitation-calcium release uncoupling in aged single human skeletal muscle fibers. J. Membarin Biol. 148, 211–222 (1995). https://doi.org/10.1007/BF00235039

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