Excitation-contraction coupling and sarcoplasmic reticulum function in mechanically skinned fibres from fast skeletal muscles of aged mice

摘要

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 ≈12 % 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 (Po) or specific force (sPo; Po 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.