External Ca(2+)-dependent excitation--contraction coupling in a population of ageing mouse skeletal muscle fibres.
In the present work, we investigate whether changes in excitation-contraction (EC) coupling mode occur in skeletal muscles from ageing mammals by examining the dependence of EC coupling on extracellular Ca(2+). Single intact muscle fibres from flexor digitorum brevis muscles from young (2-6 months) and old (23-30 months) mice were subjected to tetanic contractile protocols in the presence and absence of external Ca(2+). Contractile experiments in the absence of external Ca(2+) show that about half of muscle fibres from old mice are dependent upon external Ca(2+) for maintaining maximal tetanic force output, while young fibres are not. Decreased force in the absence of external Ca(2+) was not due to changes in charge movement as revealed by whole-cell patch-clamp experiments. Ca(2+) transients, measured by fluo-4 fluorescence, declined in voltage-clamped fibres from old mice in the absence of external Ca(2+). Similarly, Ca(2+) transients declined in parallel with tetanic contractile force in single intact fibres. Examination of inward Ca(2+) current and of mRNA and protein assays suggest that these changes in EC coupling mode are not due to shifts in dihydropyridine receptor (DHPR) and/or ryanodine receptor (RyR) isoforms. These results indicate that a change in EC coupling mode occurs in a population of fibres in ageing skeletal muscle, and is responsible for the age-related dependence on extracellular Ca(2+).
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. odelbono@wfubmc.edu.
Anthony Michael
AM
Payne
Zhenlin
Z
Zheng
Estela
E
González
Zhong-Min
ZM
Wang
María Laura
ML
Messi
Osvaldo
O
Delbono
D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D009119:Muscle Contraction / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism
D020746:Calcium Channels, L-Type; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium