Increased CaVβ1a expression with aging contributes to skeletal muscle weakness

• Published in: Aging cell Vol. 8; no. 5; pp. 584 - 594
• Main Authors: Taylor, Jackson R., Zheng, Zhenlin, Wang, Zhong‐Min, Payne, Anthony M., Messi, María L., Delbono, Osvaldo
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-10-2009
• Subjects: calcium; calcium channel; dihydropyridine receptor; excitation–contraction coupling; sarcopenia; specific force
• ISSN: 1474-9718; 1474-9726
• DOI: 10.1111/j.1474-9726.2009.00507.x

Summary
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 α1s (CaV1.1) and β1a (CaVβ1a) subunits, both of which are necessary for E‐C coupling to occur. While previous studies have found CaV1.1 expression declines in old rodents, CaVβ1a expression has not been previously examined in aging models. Western blot analysis shows a substantial increase of CaVβ1a expression over the full lifespan of Friend Virus B (FVB) mice. To examine the specific effects of CaVβ1a overexpression, a CaVβ1a‐YFP plasmid was electroporated in vivo into young animals. The resulting increase in expression of CaVβ1a corresponded to decline of CaV1.1 over the same time period. YFP fluorescence, used as a measure of CaVβ1a‐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 CaVβ1a‐YFP electroporated muscle fibers compared with sham‐electroporated, age‐matched controls. siRNA interference of CaVβ1a in young muscles reduced charge movement, while charge movement in old was restored to young control levels. These studies imply CaVβ1a serves as both a positive and negative regulator CaV1.1 expression, and that endogenous overexpression of CaVβ1a during old age may play a role in the loss of specific force.