Oligomeric status of the dihydropyridine receptor in aged skeletal muscle

摘要

A prominent feature of aging is represented by a de-crease in muscle mass and strength. Abnormalities in Ca25-regulatory membrane complexes are involved in many muscular disorders. In analogy, we determined potential age-related changes in a key component of excitation-contraction coupling, the dihydropyridine re-ceptor. Immunoblotting of the microsomal fraction from aged rabbit muscle revealed a drastic decline in the voltage-sensing ai-subunit of this transverse-tubular re-ceptor, but only marginally altered expression of its aux-iliary a2-subunit and the Na~+/K~+-ATPase. A shift to slower fibre type characteristics was indicated by an age-related increase in the slow calsequestrin isoform. Chemical crosslinking analysis showed that the triad receptor complex has a comparable tendency of protein-protein interactions in young and aged muscles. Hence, a reduced expression and not modified oligomerization of the principal dihydropyridine receptor subunit might be involved in triggering impaired triadic signal trans-duction and abnormal Ca2~-homeostasis resulting in a progressive functional decline of skeletal muscles.