Increased CaVbeta1A expression with aging contributes to skeletal muscle weakness

Aging Cell. 2009 Sep;8(5):584-94. doi: 10.1111/j.1474-9726.2009.00507.x. Epub 2009 Aug 5.


Ca2+ release from the sarcoplasmic reticulum (SR) into the cytosol is a crucial part of excitation-contraction (E-C) coupling. Excitation-contraction uncoupling, a deficit in Ca2+ release from the SR, is thought to be responsible for at least some of the loss in specific force observed in aging skeletal muscle. Excitation-contraction uncoupling may be caused by alterations in expression of the voltage-dependent calcium channel alpha1s (CaV1.1) and beta1a (CaVbeta1a) subunits, both of which are necessary for E-C coupling to occur. While previous studies have found CaV1.1 expression declines in old rodents, CaVbeta1a expression has not been previously examined in aging models. Western blot analysis shows a substantial increase of CaVbeta1a expression over the full lifespan of Friend Virus B (FVB) mice. To examine the specific effects of CaVbeta1a overexpression, a CaVbeta1a-YFP plasmid was electroporated in vivo into young animals. The resulting increase in expression of CaVbeta1a corresponded to decline of CaV1.1 over the same time period. YFP fluorescence, used as a measure of CaVbeta1a-YFP expression in individual fibers, also showed an inverse relationship with charge movement, measured using the whole-cell patch-clamp technique. Specific force was significantly reduced in young CaVbeta1a-YFP electroporated muscle fibers compared with sham-electroporated, age-matched controls. siRNA interference of CaVbeta1a in young muscles reduced charge movement, while charge movement in old was restored to young control levels. These studies imply CaVbeta1a serves as both a positive and negative regulator CaV1.1 expression, and that endogenous overexpression of CaVbeta1a during old age may play a role in the loss of specific force.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Aging / physiology*
  • Animals
  • Calcium / metabolism*
  • Calcium Channels, L-Type / genetics*
  • Cytosol / physiology
  • Electroporation
  • Gene Expression Regulation, Developmental*
  • Hindlimb
  • Mice
  • Motor Activity / physiology
  • Muscle Contraction / physiology
  • Muscle Fibers, Skeletal / physiology
  • Muscle Weakness / physiopathology*
  • Muscle, Skeletal / growth & development*
  • Muscle, Skeletal / physiology*
  • Muscle, Skeletal / physiopathology
  • Protein Subunits / genetics
  • Sarcoplasmic Reticulum / physiology


  • Actins
  • Cacnb1 protein, mouse
  • Calcium Channels, L-Type
  • Protein Subunits
  • Calcium