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

The cardiac voltage-gated sodium channel, Nav1.5, plays a central role in cardiac excitability and impulse propagation and associates with the dystrophin multiprotein complex (DMC) at the lateral membrane of cardiomyocytes. It was previously shown that Nav1.5 protein content and the sodium current (...

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Main Authors: Jean-Sebastien eRougier, Bruno eGavillet, Hugues eAbriel
Format: Article
Language:English
Published: Frontiers Media S.A. 2013-03-01
Series:Frontiers in Physiology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fphys.2013.00051/full
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author Jean-Sebastien eRougier
Bruno eGavillet
Hugues eAbriel
author_facet Jean-Sebastien eRougier
Bruno eGavillet
Hugues eAbriel
author_sort Jean-Sebastien eRougier
collection DOAJ
description The cardiac voltage-gated sodium channel, Nav1.5, plays a central role in cardiac excitability and impulse propagation and associates with the dystrophin multiprotein complex (DMC) at the lateral membrane of cardiomyocytes. It was previously shown that Nav1.5 protein content and the sodium current (INa) were both decreased in cardiomyocytes of dystrophin-deficient mdx5cv mice. In this study, wild-type (WT) and mdx5cv 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 Nav1.5 protein and INa 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 Nav1.5 in dystrophin-deficient cells is dependent on proteasomal degradation.
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spelling doaj.art-8c3afb58444d4855823ab142810b24942022-12-22T02:58:13ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2013-03-01410.3389/fphys.2013.0005142786Proteasome inhibitor (MG132) rescues Nav1.5 protein content and the cardiac sodium current in dystrophin-deficient mdx5cv miceJean-Sebastien eRougier0Bruno eGavillet1Hugues eAbriel2University of Bern: UNIBEUniversity of Bern: UNIBEUniversity of Bern: UNIBEThe cardiac voltage-gated sodium channel, Nav1.5, plays a central role in cardiac excitability and impulse propagation and associates with the dystrophin multiprotein complex (DMC) at the lateral membrane of cardiomyocytes. It was previously shown that Nav1.5 protein content and the sodium current (INa) were both decreased in cardiomyocytes of dystrophin-deficient mdx5cv mice. In this study, wild-type (WT) and mdx5cv 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 Nav1.5 protein and INa 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 Nav1.5 in dystrophin-deficient cells is dependent on proteasomal degradation.http://journal.frontiersin.org/Journal/10.3389/fphys.2013.00051/fullDystrophinElectrophysiologySodium ChannelsinhibitorsProteasome
spellingShingle Jean-Sebastien eRougier
Bruno eGavillet
Hugues eAbriel
Proteasome inhibitor (MG132) rescues Nav1.5 protein content and the cardiac sodium current in dystrophin-deficient mdx5cv mice
Frontiers in Physiology
Dystrophin
Electrophysiology
Sodium Channels
inhibitors
Proteasome
title Proteasome inhibitor (MG132) rescues Nav1.5 protein content and the cardiac sodium current in dystrophin-deficient mdx5cv mice
title_full Proteasome inhibitor (MG132) rescues Nav1.5 protein content and the cardiac sodium current in dystrophin-deficient mdx5cv mice
title_fullStr Proteasome inhibitor (MG132) rescues Nav1.5 protein content and the cardiac sodium current in dystrophin-deficient mdx5cv mice
title_full_unstemmed Proteasome inhibitor (MG132) rescues Nav1.5 protein content and the cardiac sodium current in dystrophin-deficient mdx5cv mice
title_short Proteasome inhibitor (MG132) rescues Nav1.5 protein content and the cardiac sodium current in dystrophin-deficient mdx5cv mice
title_sort proteasome inhibitor mg132 rescues nav1 5 protein content and the cardiac sodium current in dystrophin deficient mdx5cv mice
topic Dystrophin
Electrophysiology
Sodium Channels
inhibitors
Proteasome
url http://journal.frontiersin.org/Journal/10.3389/fphys.2013.00051/full
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