Ca(2+) permeation and/or binding to CaV1.1 fine-tunes skeletal muscle Ca(2+) signaling to sustain muscle function.
Chang Seok Lee, Adan Dagnino-Acosta, Viktor Yarotskyy, Amy Hanna, Alla Lyfenko, Mark Knoblauch, Dimitra K Georgiou, Ross A Poché, Michael W Swank, Cheng Long, Iskander I Ismailov, Johanna Lanner, Ted Tran, KeKe Dong, George G Rodney, Mary E Dickinson, Christine Beeton, Pumin Zhang, Robert T Dirksen, Susan L Hamilton
文献索引:Skelet. Muscle 5 , 4, (2015)
全文:HTML全文
摘要
Ca(2+) influx through CaV1.1 is not required for skeletal muscle excitation-contraction coupling, but whether Ca(2+) permeation through CaV1.1 during sustained muscle activity plays a functional role in mammalian skeletal muscle has not been assessed.We generated a mouse with a Ca(2+) binding and/or permeation defect in the voltage-dependent Ca(2+) channel, CaV1.1, and used Ca(2+) imaging, western blotting, immunohistochemistry, proximity ligation assays, SUnSET analysis of protein synthesis, and Ca(2+) imaging techniques to define pathways modulated by Ca(2+) binding and/or permeation of CaV1.1. We also assessed fiber type distributions, cross-sectional area, and force frequency and fatigue in isolated muscles.Using mice with a pore mutation in CaV1.1 required for Ca(2+) binding and/or permeation (E1014K, EK), we demonstrate that CaV1.1 opening is coupled to CaMKII activation and refilling of sarcoplasmic reticulum Ca(2+) stores during sustained activity. Decreases in these Ca(2+)-dependent enzyme activities alter downstream signaling pathways (Ras/Erk/mTORC1) that lead to decreased muscle protein synthesis. The physiological consequences of the permeation and/or Ca(2+) binding defect in CaV1.1 are increased fatigue, decreased fiber size, and increased Type IIb fibers.While not essential for excitation-contraction coupling, Ca(2+) binding and/or permeation via the CaV1.1 pore plays an important modulatory role in muscle performance.
相关化合物
相关文献:
2015-02-20
[Oncotarget 6(5) , 2604-14, (2015)]
2014-01-01
[PLoS ONE 9(12) , e116152, (2014)]
2015-05-01
[Biomaterials 51 , 1-11, (2015)]
2015-04-01
[J. Pineal Res. 58(3) , 310-20, (2015)]
2015-04-22
[J. Ethnopharmacol. 164 , 265-72, (2015)]