Renganathan M, Messi M L, Schwartz R, Delbono O
Department of Internal Medicine, Gerontology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
FEBS Lett. 1997 Nov 3;417(1):13-6. doi: 10.1016/s0014-5793(97)01225-8.
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 alpha1 subunit expression in adult skeletal muscle.
二氢吡啶受体（DHPR）和肌浆网（SR）Ca2+释放通道（RyR1）的数量及其相互作用决定了肌膜兴奋 - SR Ca2+释放 - 收缩偶联（ECC）的效能。在各种动物物种和肌肉亚型中所证实的那样，这两种受体在ECC中都起着核心作用。在本研究中，我们研究了人胰岛素样生长因子1（hIGF-1）转基因过表达对成年C57BL/6小鼠趾长伸肌（EDL）（快肌）、比目鱼肌（慢肌）以及快、慢肌混合样本中这两种Ca2+通道水平的影响。hIGF-1转基因小鼠的肌肉显示IGF-1浓度显著增加（20 - 30倍），DHPR数量增加（52%），而未检测到RyR1结合位点有显著变化。对DHPR和RyR1的不同影响导致DHPR/RyR1比值增加30%。快肌和慢肌中DHPR数量分别增加50%和70%，DHPR/RyR1分别增加30%和80%。这些结果支持了这样一种观点，即hIGF-1自分泌/旁分泌分泌增加对成年骨骼肌中DHPR α1亚基表达具有强大的刺激作用。
