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.
Plant
David R
DR
Department of Physiology, The University of Melbourne, Victoria 3010, Australia.
Lynch
Gordon S
GS
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