Proteasome inhibitor (MG132) rescues Na(v)1.5 protein content and the cardiac sodium current in dystrophin-deficient mdx(5cv) mice

The cardiac voltage-gated sodium channel, Na(v)1.5, plays a central role in cardiac excitability and impulse propagation and associates with the dystrophin multiprotein complex at the lateral membrane of cardiomyocytes. It was previously shown that Na(v)1.5 protein content and the sodium current (l(Na)) were both decreased in cardiomyocytes of dystrophin-deficient mdx(5cv) mice. In this study, wild-type and mdx(5cv) mice were treated for 7 days with the proteasome inhibitor MG132 (10 μg/Kg/24 h) using implanted osmotic mini pumps. MG132 rescued both the total amount of Na(v)1.5 protein and l(Na) but, unlike in previous studies, de novo expression of dystrophin was not observed in skeletal or cardiac muscle. This study suggests that the reduced expression of Na(v)1.5 in dystrophin-deficient cells is dependent on proteasomal degradation.