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

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Abstract
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.