Age-Dependent Expression of CaVâ1a Subunit in Skeletal Muscle. (Poster)

JACKSON TAYLOR; RAMÓN JIMENEZ-MORENO; MESSI L; ZHONG-MIN WANG; HANG SHI; HEREÑU C; ´DELBONO OSVALDO

Boston USA

Congreso; Annual Meeting of the Biophysical Society - Sociedad Anual de Biofísica, Febrero 28-Marzo 4 del 2009; 2009

Jackson Taylor1,2, Ramón Jimenez-Moreno1, María L. Messi1, Zhong-Min Wang1, Hang Shi1 Claudia Hereñú3, and Osvaldo Delbono1,2 Department of Internal Medicine-Gerontology1, Neuroscience Program2 Wake Forest University School of Medicine, Winston-Salem, North Carolina Department of Histology, National University of La Plata, La Plata, Argentina3 E-C uncoupling, a deficit in Ca2+ release from the sarcoplasmic reticulum, is thought to be responsible for some of the loss in specific force associated with aging (Delbono et al., 1995).    E-C uncoupling may be caused by alterations in the expression of voltage-dependent calcium channel α1s (CaV1.1) and β1a (CaVβ1a) subunits. CaVβ subunits are classically known for their role augmenting CaVα1 subunit trafficking (Bichet et al., 2000) and their necessity for E-C coupling to occur in skeletal muscle (Gregg et al., 1996). Recent studies suggest CaVβ subunits also work to decrease the expression of several CaVα1 isoforms at the plasma membrane (Beguin et al., 2001; Gonzalez-Gutierrez et al., 2007). Overexpression of CaVβ1a with aging has recently been implicated by our laboratory as a negative regulator of CaV1.1 membrane expression, an effect which contributes to a loss of specific force in muscle. Conclusions: fiber type. This is likely to be caused at least in part by a significant and concomitant increase in CaVβ1a mRNA levels with age. CaVβ1a protein levels also appear to increase with age in humans. CaVβ1a is detectable in pure nuclear fractions, where it is present at very high levels in old muscle. As previously shown, CaVβ1a overexpression corresponds to reduced charge movement and thus CaV1.1 expression. RAd-CaVβ1a-YFP provides an effective reproduction both in vitro and in vivo of age-related CaVβ1a overexpression. CaVβ1a appears to be overexpressed somewhat ubiquitously throughout cytosol, membrane, and nucleus of muscle fibers.