Résumé :
|
Skeletal muscles from young adult mice containing homozygous deletion of the gene for the sarcoplasmic reticulum protein JP-45 were studied and compared to age-matched wild-type litter mates. Analysis of spontaneous motor activity with a running wheel revealed that dark phase running distance ran by the JP-45 KO mice was significantly lower compared to wild type. In vitro EDL and soleus muscle mechanical property analysis showed slower twitch and tetanic absolute and specific force in JP-45 KO mice compared to wild-type, while muscle size, wet weight and cross sectional area of muscle fibers were not different. Isolated sarcotubular membranes isolated from 3 month and 6 months old JP-45 KO mouse muscles exhibited reduced [H3]PN200-110 binding indicating down regulation of CaV1.1 protein. SR Ca2+ release in voltage-clamped muscle fibers of JP-45 KO was significantly reduced compared to wild-type. Our results show that ablation of JP-45 reduces functional CaV1.1 protein expression and/or targeting to the t-tubule membrane, impairing the EC coupling signal between CaV1.1 and RyR1, thereby reducing skeletal muscle force
|