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

• Published in: The Journal of membrane biology Vol. 148; no. 3; p. 211
• Main Authors: Delbono, O, O'Rourke, K S, Ettinger, W H
• Format: Journal Article
• Language: English
• Published: United States 01.12.1995
• Subjects: Adult; Aged; Aging - physiology; Animals; Biological Transport; Biopsy, Needle; Calcium - physiology; Calcium Channels - physiology; Calcium Channels, L-Type; Female; Humans; Male; Muscle Contraction - physiology; Muscle Denervation; Muscle Fibers, Fast-Twitch - physiology; Muscle Weakness - physiopathology; Muscle, Skeletal - pathology; Muscle, Skeletal - physiopathology; Patch-Clamp Techniques; Rats; Tetrodotoxin - pharmacology
• ISSN: 0022-2631; 1432-1424
• DOI: 10.1007/BF00235039

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/muF 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 muA/muF for young and old fibers, respectively (P < 0.01). The peak calcium transient studied with mag-fura-2 (400 microM) was 6.3 +/- 0.4 microM and 4.2 +/- 0.3 microM 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.