Figure 4.

Effects of increased calcium cycling on cardiac myocytes with dystrophin deficiency. Loss of dystrophin destabilizes the sarcolemma and leads to calcium mishandling and overload. Increasing calcium cycling via modulation of Serca2a/PLN function increases calcium uptake into the SR, which could decrease cytosolic calcium concentration. However, increased calcium cycling also increases contractility, which could subsequently cause increased membrane damage and exacerbate calcium overload. In the context of dystrophin deficiency, phospholamban (PLN) ablation led to increased membrane damage and worsened cardiomyopathy [19].