Sarcoplasmic reticulum Ca2+ handling in young DBA/2J vs C57BL/10 mdx models of Duchenne muscular dystrophy

Abstract

SummaryThe DBA/2J (D2) mdx mouse has emerged as a more severe model of Duchenne muscular dystrophy when compared to the traditional C57BL/10 (C57) mdx mouse. Here, we questioned whether sarcoplasmic reticulum (SR) Ca2+ handling would differ in muscles from young D2 and C57 mdx mice. Our results show that only D2 mdx mice had impaired SR Ca2+ uptake; however, both D2- and C57 mdx mice had impairments in SR Ca2+ leak, which was associated with lowered ryanodine receptor content. To further examine the impairments in SR Ca2+uptake, Ca2+-dependent SERCA activity assays were performed which showed that only the D2 mdx, but not C57 mdx mice had drastic impairments in SERCA-mediated ATP hydrolysis. Further, D2 mice had greater activation of the Ca2+-activated protease, calpain. Overall, our study demonstrates that that SR Ca2+ handling is impaired early on in the D2 mdx mouse, specifically at the level of the SERCA pump.