Reduced expression of sarcalumenin and related Ca2+-regulatory proteins in aged rat skeletal muscle

In skeletal muscle, Ca2+-cycling through the sarcoplasm regulates the excitation–contraction–relaxation cycle. Since uncoupling between sarcolemmal excitation and fibre contraction may play a key role in the functional decline of aged muscle, this study has evaluated the expression levels of key Ca2+-handling proteins in senescent preparations using immunoblotting and confocal microscopy. Sarcalumenin, a major luminal Ca2+-binding protein that mediates ion shuttling in the longitudinal sarcoplasmic reticulum, was found to be greatly reduced in aged rat tibialis anterior, gastrocnemius and soleus muscle as compared to adult specimens. Minor sarcolemmal components of Ca2+-extrusion, such as the surface Ca2+-ATPase and the Na+–Ca2+-exchanger, were also diminished in senescent fibres. No major changes were observed for calsequestrin, sarcoplasmic reticulum Ca2+-ATPase and the ryanodine receptor Ca2+-release channel. In contrast, the age-dependent reduction in the α1S-subunit of the dihydropryridine receptor was confirmed. Hence, this report has shown that downstream from the well-established defect in coupling between the t-tubular voltage sensor and the junctional Ca2+-release channel complex, additional age-related alterations exist in the expression of essential Ca2+-handling proteins. This may trigger abnormal luminal Ca2+-buffering and/or decreased plasmalemmal Ca2+-removal, which could exacerbate impaired signaling or disturbed intracellular ion balance in aged fibres, thereby causing contractile weakness.