Depletion of Ca2+ in the sarcoplasmic reticulum stimulates Ca2+ entry into mouse skeletal muscle fibres

J Physiol. 2001 May 15;533(Pt 1):185-99. doi: 10.1111/j.1469-7793.2001.0185b.x.


To examine whether a capacitative Ca2+ entry pathway is present in skeletal muscle, thin muscle fibre bundles were isolated from extensor digitorum longus (EDL) muscle of adult mice, and isometric tension and fura-2 signals were simultaneously measured. The sarcoplasmic reticulum (SR) in the muscle fibres was successfully depleted of Ca2+ by repetitive treatments with high-K+ solutions, initially in the absence and then in the presence of a sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor. Depletion of the SR of Ca2+ enabled us for the first time to show convincingly that the vast majority of the voltage-sensitive Ca2+ store overlaps the caffeine-sensitive Ca2+ store in intact fibres from mouse EDL muscle. This conclusion was based on the observation that both high-K+ solution and caffeine failed to cause a contracture in the depleted muscle fibres. The existence of a Ca2+ influx pathway active enough to refill the depleted SR within several minutes was shown in skeletal muscle fibres. Ca2+ entry was sensitive to Ni2+, but resistant to nifedipine and was suppressed by plasma membrane depolarisation. Evidence for store-operated Ca2+ entry was provided by measurements of Mn2+ entry. Significant acceleration of Mn2+ entry was observed only when the SR was severely depleted of Ca2+. The Mn2+ influx, which was blocked by Ni2+ but not by nifedipine, was inwardly rectifying, as is the case with the Ca2+ entry. These results indicate that the store-operated Ca2+ entry is similar to the Ca2+ release-activated Ca2+ channel (CRAC) current described in other preparations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport / drug effects
  • Biological Transport / physiology
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, L-Type / metabolism
  • Calcium-Transporting ATPases / antagonists & inhibitors
  • Calcium-Transporting ATPases / metabolism
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Hydroquinones / pharmacology
  • In Vitro Techniques
  • Indoles / pharmacology
  • Manganese / pharmacokinetics
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mice
  • Muscle Fibers, Fast-Twitch / metabolism*
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism*
  • Nifedipine / pharmacology
  • Potassium / pharmacology
  • Sarcoplasmic Reticulum / metabolism*
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Thapsigargin / pharmacology


  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Enzyme Inhibitors
  • Hydroquinones
  • Indoles
  • 2,5-di-tert-butylhydroquinone
  • Manganese
  • Thapsigargin
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Calcium-Transporting ATPases
  • Nifedipine
  • Potassium
  • Calcium
  • cyclopiazonic acid