Oligomeric status of the dihydropyridine receptor in aged skeletal muscle.
A prominent feature of aging is represented by a decrease in muscle mass and strength. Abnormalities in Ca2+ -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 receptor. Immunoblotting of the microsomal fraction from aged rabbit muscle revealed a drastic decline in the voltage-sensing alpha1-subunit of this transverse-tubular receptor, but only marginally altered expression of its auxiliary alpha(2)-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 transduction and abnormal Ca2+ -homeostasis resulting in a progressive functional decline of skeletal muscles.
Ryan
M
M
Department of Pharmacology, University College Dublin, Dublin, Belfield, 4, Ireland.
Carlson
B M
BM
Ohlendieck
K
K
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000937:Antigen-Antibody Reactions / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000737:chemistry* / Q000378:metabolism*; D002155:Calsequestrin / Q000032:analysis; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000494:pharmacology; D015151:Immunoblotting; D007425:Intracellular Membranes / Q000737:chemistry; D008297:Male; D008861:Microsomes / Q000737:chemistry / Q000187:drug effects; D008970:Molecular Weight; D018656:Muscle Fibers, Fast-Twitch / Q000737:chemistry; D018657:Muscle Fibers, Slow-Twitch / Q000737:chemistry; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000378:metabolism*; D020033:Protein Isoforms / Q000032:analysis; D021122:Protein Subunits; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry / Q000378:metabolism; D013388:Succinimides / Q000737:chemistry / Q000494:pharmacology
D020746:Calcium Channels, L-Type; D002155:Calsequestrin; D003432:Cross-Linking Reagents; D020033:Protein Isoforms; D021122:Protein Subunits; D013388:Succinimides; D000254:Sodium-Potassium-Exchanging ATPase; C011240:dithiobis(succinimidylpropionate); D002118:Calcium