title: Excitation-calcium release uncoupling in aged single human skeletal muscle fibers.
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/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.
authors: Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
authors: O
authors: O
authors: Delbono
authors: K S
authors: KS
authors: O'Rourke
authors: W H
authors: WH
authors: Ettinger
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D000818:Animals; D001692:Biological Transport; D001707:Biopsy, Needle; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D020746:Calcium Channels, L-Type; D005260:Female; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009121:Muscle Denervation; D018656:Muscle Fibers, Fast-Twitch / Q000502:physiology*; D018908:Muscle Weakness / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D051381:Rats; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D013779:Tetrodotoxin; D002118:Calcium