Excitation-contraction coupling and sarcoplasmic reticulum function in mechanically skinned fibres from fast skeletal muscles of aged mice.
Ageing is generally associated with a decline in skeletal muscle mass and strength, and a slowing of muscle contraction, factors that impact upon the quality of life for the elderly. Alterations in Ca2+ handling are thought to contribute to these age-related changes in muscle contractility, yet the effects of ageing on sarcoplasmic reticulum (SR) Ca2+ handling and the Ca2+ transport system remain unresolved. We used mechanically skinned single fibres from the fast twitch extensor digitorum longus (EDL) muscles from young (4-month-old) and old (27- to 28-month-old) mice to test the hypothesis that the age-related changes in skeletal muscle contractility, especially the slower rate of contraction, are due to changes intrinsic to the muscle fibres. There were no age-related differences in the peak height of depolarization-induced contractile response (DICR) or the number of DICRs elicited before rundown (DICR < 50 % of initial). The time taken to reach peak DICR (TPDICR) was approximately12 % slower in single muscle fibres from old compared with young mice (P < 0.05). The rate of relaxation following DICR was not different in young and old mice. Examination of SR function demonstrated that SR Ca2+ reloading in Ca2+ -depleted skinned fibres was not different in young and old mice, nor was there any age-related difference in Ca2+ leak from the SR. However, low [caffeine] contracture in fibres from old mice was only half of that observed in fibres from young mice (P < 0.05), indicating a lower sensitivity of the SR Ca2+ release channel (CRC) to caffeine. We found no difference in maximum Ca2+ -activated force (P(o)) or specific force (sP(o); P(o) corrected for cross-sectional area) in EDL muscle fibres from young and old mice. Impaired excitation-contraction (E-C) coupling and a decrease in SR CRC function are mechanisms which are likely to contribute to the overall slowing of muscle contraction with age.
Department of Physiology, The University of Melbourne, Victoria 3010, Australia.
David R
DR
Plant
Gordon S
GS
Lynch
D000375:Aging / Q000502:physiology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018656:Muscle Fibers, Fast-Twitch / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000502:physiology*
D010726:Phosphodiesterase Inhibitors; D002110:Caffeine; D002118:Calcium