Compromised store‐operated Ca entry (SOCE) in aged skeletal muscle

Abstract

In aged skeletal muscle, changes in contractile apparatus function cannot fully explain the observed decrease in specific force. Since extracellular Ca entry appears to help maintain normal contractile function in skeletal muscle during development and regeneration, our goal in this study was to evaluate the functional status of store-operated Ca entry (SOCE) in aged skeletal muscle. We employed the Mn-quenching of Fura-2 fluorescence to monitor SOCE in intact flexor digitorium brevis (FDB) muscle fibers isolated from young (2–5 month old) and aged mice (26–27 month old). SOCE activation was initiated following depletion of the sarcoplasmic reticulum (SR) Ca store using a combination of caffeine (10 mM) and ryanodine (10 μM) in an extracellular solution containing 0 Ca. The rate of Fura-2 quenching by Mn was significantly smaller in aged FDB muscle compared with that in young FDB muscle, indicating compromised function of SOCE associated with muscle aging. In an independent assay, we applied our recently developed confocal-microscopy based method to measure the spatial and temporal aspects of SOCE activation in individual extensor digitorum longus (EDL) muscle fibers following mechanical skinning (Zhao et al., Physiol. Genomics, 2005). We found that Ca transport across the sealed transverse-tubule membrane compartments following depletion of the SR Ca store is also significantly reduced in aged EDL muscle fibers. Therefore, our data demonstrate that SOCE is significantly compromised in aged skeletal muscle, which may contribute to the reduced contractile function in aged skeletal muscle.