External Ca(2+)-dependent excitation--contraction coupling in a population of ageing mouse skeletal muscle fibres

J Physiol. 2004 Oct 1;560(Pt 1):137-55. doi: 10.1113/jphysiol.2004.067322. Epub 2004 Aug 5.


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+).

Publication types

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

MeSH terms

  • Aging / physiology*
  • Animals
  • Calcium / metabolism*
  • Calcium / pharmacology
  • Calcium Channels, L-Type / metabolism
  • Mice
  • Mice, Inbred DBA
  • Muscle Contraction / physiology*
  • Muscle Fibers, Skeletal / physiology*
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / physiology*
  • Patch-Clamp Techniques
  • Ryanodine Receptor Calcium Release Channel / metabolism


  • Calcium Channels, L-Type
  • Ryanodine Receptor Calcium Release Channel
  • Calcium