Unregulated Ca2+ Cycling Exacerbates DMD Cardiomyopathy

Does improving intracellular calcium handling through cardiac-specific phospholamban ablation in a mouse model of Duchenne Muscular Dystrophy affect the development of cardiomyopathy? In this podcast, Associate Editor Junichi Sadoshima (Rutgers New Jersey Medical School) interviews first author Michelle Law (University of Minnesota) and content expert Sakthivel Sadayappan (University of Cincinnati) about the new study by Law and co-authors. Using the mdx mouse model, phospholamban ablation was studied in the context of dystrophic cardiomyopathy. Law et al found that although calcium cycling was enhanced in myocytes, DMD cardiomyopathy was surprisingly worsened in vivo. Given that there are both calcium mishandling and mechanical stress components to DMD cardiomyopathy, do the authors suspect that unregulated Serca2a pump function damaged the sarcolemma and increased fibrosis and myocyte death? Listen and find out.

 

Michelle L Law, Kurt W Prins, Megan E Olander, and Joseph M Metzger Exacerbation of dystrophic cardiomyopathy by phospholamban deficiency-mediated chronically increased cardiac Ca2+ cycling in vivo Am J Physiol Heart Circ Physiol, published August 17, 2018. DOI: 10.1152/ajpheart.00341.2018