Dysferlin deficiency blunts β‐adrenergic‐dependent lusitropic function of mouse heart

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp6867-list-0001">Deficiency of dysferlin causes limb‐girdle muscular dystrophy 2B and Miyoshi myopathy with cardiac involvement that leads to dilated cardiomyopathy and heart failure. The pathogenesis and pathophysiology of dysferlin cardiomyopathy are not fully understood.We studied cardiac phenotypes of young dysferlin gene knockout mice to investigate the primary pathological and pathophysiological changes.In comparison with wild‐type controls, dysferlin‐deficient cardiomyocytes showed slower Ca²⁺ re‐sequestration, and dysferlin deficiency blunted the β‐adrenergic effect on relaxation and pumping function of ex vivo working hearts.Dysferlin deficiency increased phosphorylation of ventricular myosin light chain 2, suggesting a compensatory response to the impaired cardiac lusitropic function.The data suggest that delayed calcium re‐sequestration and post‐translational modification of myofilament proteins may provide potential targets to develop new treatments for dysferlin cardiomyopathy.