AUTHOR=Rougier Jean-Sebastien , Gavillet Bruno , Abriel Hugues 

TITLE=Proteasome inhibitor (MG132) rescues Nav1.5 protein content and the cardiac sodium current in dystrophin-deficient mdx5cv mice

JOURNAL=Frontiers in Physiology

VOLUME=4

YEAR=2013

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2013.00051

DOI=10.3389/fphys.2013.00051

ISSN=1664-042X

ABSTRACT=<p>The cardiac voltage-gated sodium channel, Na<sub>v</sub>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<sub>v</sub>1.5 protein content and the sodium current (<italic>l</italic><sub>Na</sub>) were both decreased in cardiomyocytes of dystrophin-deficient mdx<sup><italic>5cv</italic></sup> mice. In this study, wild-type and mdx<sup><italic>5cv</italic></sup> 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<sub>v</sub>1.5 protein and <italic>l</italic><sub>Na</sub> but, unlike in previous studies, <italic>de novo</italic> expression of dystrophin was not observed in skeletal or cardiac muscle. This study suggests that the reduced expression of Na<sub>v</sub>1.5 in dystrophin-deficient cells is dependent on proteasomal degradation.</p>