OVEREXPRESSION OF HIGF-1 EXCLUSIVELY IN SKELETAL-MUSCLE INCREASES THENUMBER OF DIHYDROPYRIDINE RECEPTORS IN ADULT TRANSGENIC MICE

The number of dihydropyridine receptors (DHPR) and sarcoplasmic reticu lum (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 demonstr ated in various animal species and muscle subtypes, In the present wor k we studied the effect of transgenic overexpression of human insulinl ike 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, Mus cles from hIGF-1 transgenic mice showed a significant increase in IGF- I 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 DHP R/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, respective ly, These results support the concept that the increased autocrine/par acrine secretion of hIGF-1 exerts potent stimulatory effects on DHPR e el subunit expression in adult skeletal muscle. (C) 1997 Federation of European Biochemical Societies.