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

FEBS Letters

Messi, M.L²  Renganathan, M³  Delbono, O²  Schwartz, R¹ 

[1] Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA;Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA;Department of Internal Medicine, Gerontology, Bowman Gray School of Medicine, Wake Forest University, Medical Center Boulevard, Winston-Salem, NC 27157, USA

关键词: Skeletal muscle;    Excitation-contraction coupling;    Insulin-like growth factor 1;    Aging;    Dihydropyridine receptor;    Ryanodine receptor;   

DOI  :  10.1016/S0014-5793(97)01225-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The number of dihydropyridine receptors (DHPR) and sarcoplasmic reticulum (SR) Ca²⁺ release channels (RyR1) and their interaction determine the efficacy of the sarcolemmal excitation-SR Ca²⁺ 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 Ca²⁺ 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.

【 授权许可】

Unknown