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

J Membr Biol. 1995 Dec;148(3):211-22. doi: 10.1007/BF00235039.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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

Substances

  • Calcium Channels
  • Calcium Channels, L-Type
  • Tetrodotoxin
  • Calcium