Age Dependent Expression of CaVβ1a Subunit in Aging Skeletal Muscle

Abstract

Ca2+ release from the sarcoplasmic reticulum (SR) into the cytosol is a crucial part of excitation-contraction (E-C) coupling. E-C 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. E-C uncoupling may be caused by alterations in the expression of voltage-dependent calcium channel α1s (CaV1.1) and β1a (CaVβ1a) subunits. In addition to its classical role augmenting CaV1.1 trafficking and function, overexpression of CaVβ1a has recently been implicated by our laboratory as a negative regulator of CaV1.1 membrane expression. While previous studies have found CaV1.1 expression declines in old rodents, CaVβ1a expression had not been examined in aging models. We conducted western blot analyses to examine CaVβ1a expression in mouse skeletal muscle at four age groups across the animal's lifespan. Investigation of CaVβ1a expression was further segregated by muscle compartment location, fiber type composition, and mouse strain. Our results show a substantial increase of CaVβ1a expression both early and very late in life of FVB mice, regardless of fiber type or location. In order to examine the specific subcellular location where this increased quantity of CaVβ1a resides, we performed immunocytochemistry on dissociated single FDB fibers. Additional western blot analyses were performed on isolated subcellular fractions from young and old animals. Together with previous data from our laboratory showing decline in CaV1.1 as a result of both, aging and CaVβ1a artificial overexpression, these studies suggest a novel role of CaVβ1a, and that endogenous overexpression of CaVβ1a during old age may contribute to the coincident loss of specific force in skeletal muscle.