L-type Ca2+ channel-insulin-like growth factor-1 receptor signaling impairment in aging rat skeletal muscle.
The present study investigates the modulation of skeletal muscle L-type Ca2+ channel receptor in response to insulin-like growth factor-1 receptor (IGF-1R) activation. Single extensor digitorum longus and multifiber preparations were isolated from 7- (young), 14- (middle-age) and 28-(old) month- Fisher 344 X Brown Norway rats. Calcium current was potentiated in fibers from young and middle-age rats due to a -13 mV shift in half-activation potential. Fibers from old animals failed to show current potentiation in response to IGF-1R activation. IGF-1 induced a ten-fold increase in the phosphorylation of the L-type Ca2+ channel alpha1 subunit in young and middle-age fibers but failed to induce phosphorylation in old fibers. Addition of 0.5 mM Ca2+ increased the IGF-1 induced phosphorylation in young and middle-age fibers three fold but not in old fibers. The tyrosine kinase inhibitor, genistein, and the PKC inhibitor peptide, 19-36, decreased IGF-1 induced phosphorylation of alpha1 subunit to 15% in young and middle-age fibers but failed to inhibit phosphorylation in old fibers. These results demonstrate that the IGF-1-L-type Ca2+ channel alpha1 subunit signaling is impaired in skeletal muscle fibers from old animals due to alterations in the trk-PKC pathway.
Renganathan
M
M
Department of Internal Medicine and Gerontology, The Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27157, USA. mrengana@bgsm.edu
Sonntag
W E
WE
Delbono
O
O
D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000254:growth & development / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D017526:Receptor, IGF Type 1 / Q000502:physiology*; D015398:Signal Transduction
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D007529:Isoflavones; D007334:Insulin-Like Growth Factor I; D019833:Genistein; D017526:Receptor, IGF Type 1; D011493:Protein Kinase C; D002118:Calcium