Overexpression of hIGF-1 exclusively in skeletal muscle increases the number of dihydropyridine receptors in adult transgenic mice

• Published in: FEBS letters Vol. 417; no. 1; pp. 13 - 16
• Main Authors: Renganathan, M, Messi, M.L, Schwartz, R, Delbono, O
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 03.11.1997
• Subjects: Aging; Animals; Calcium Channels - metabolism; Calcium Channels, L-Type; Dihydropyridine receptor; Excitation-contraction coupling; Gene Expression; Humans; Insulin-like growth factor 1; Insulin-Like Growth Factor I - biosynthesis; Insulin-Like Growth Factor I - genetics; Mice; Mice, Inbred C57BL; Mice, Transgenic; Muscle, Skeletal - metabolism; Ryanodine receptor; Ryanodine Receptor Calcium Release Channel - metabolism; Skeletal muscle; Aging; Excitation-contraction coupling; Dihydropyridine receptor; Insulin-like growth factor 1; Skeletal muscle; Ryanodine receptor
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(97)01225-8

The number of dihydropyridine receptors (DHPR) and sarcoplasmic reticulum (SR) Ca 2+ release channels (RyR1) and their interaction determine the efficacy of the sarcolemmal excitation-SR Ca 2+ release-contraction coupling (ECC). Both receptors play a central role in ECC as demonstrated in various animal species and muscle subtypes. In the present work we studied the effect of transgenic overexpression of human insulin-like growth factor 1 (hIGF-1) on the levels of these two Ca 2+ channels in extensor digitorum longus (EDL) (fast-twitch), soleus (slow-twitch) and pool of fast- and slow-twitch muscles from adult C57BL/6 mice. Muscles from hIGF-1 transgenic mice showed a significant increase in IGF-1 concentration (20–30-fold) and in the number of DHPR (52% increase) whereas no significant change in RyR1 binding sites was detected. The differential effect on DHPR and RyR1 resulted in a 30% increase in DHPR/RyR1 ratio. Fast- and slow-twitch muscles showed 50 and 70% increase in the number of DHPR and 30 and 80% increase in DHPR/RyR1, respectively. These results support the concept that the increased autocrine/paracrine secretion of hIGF-1 exerts potent stimulatory effects on DHPR α1 subunit expression in adult skeletal muscle.