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Voltage-gated Na(v) channel targeting in the heart requires an ankyrin-G–dependent cellular pathway

Voltage-gated Na(v) channels are required for normal electrical activity in neurons, skeletal muscle, and cardiomyocytes. In the heart, Na(v)1.5 is the predominant Na(v) channel, and Na(v)1.5-dependent activity regulates rapid upstroke of the cardiac action potential. Na(v)1.5 activity requires prec...

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Autores principales: Lowe, John S., Palygin, Oleg, Bhasin, Naina, Hund, Thomas J., Boyden, Penelope A., Shibata, Erwin, Anderson, Mark E., Mohler, Peter J.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213608/
https://www.ncbi.nlm.nih.gov/pubmed/18180363
http://dx.doi.org/10.1083/jcb.200710107
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author Lowe, John S.
Palygin, Oleg
Bhasin, Naina
Hund, Thomas J.
Boyden, Penelope A.
Shibata, Erwin
Anderson, Mark E.
Mohler, Peter J.
author_facet Lowe, John S.
Palygin, Oleg
Bhasin, Naina
Hund, Thomas J.
Boyden, Penelope A.
Shibata, Erwin
Anderson, Mark E.
Mohler, Peter J.
author_sort Lowe, John S.
collection PubMed
description Voltage-gated Na(v) channels are required for normal electrical activity in neurons, skeletal muscle, and cardiomyocytes. In the heart, Na(v)1.5 is the predominant Na(v) channel, and Na(v)1.5-dependent activity regulates rapid upstroke of the cardiac action potential. Na(v)1.5 activity requires precise localization at specialized cardiomyocyte membrane domains. However, the molecular mechanisms underlying Na(v) channel trafficking in the heart are unknown. In this paper, we demonstrate that ankyrin-G is required for Na(v)1.5 targeting in the heart. Cardiomyocytes with reduced ankyrin-G display reduced Na(v)1.5 expression, abnormal Na(v)1.5 membrane targeting, and reduced Na(+) channel current density. We define the structural requirements on ankyrin-G for Na(v)1.5 interactions and demonstrate that loss of Na(v)1.5 targeting is caused by the loss of direct Na(v)1.5–ankyrin-G interaction. These data are the first report of a cellular pathway required for Na(v) channel trafficking in the heart and suggest that ankyrin-G is critical for cardiac depolarization and Na(v) channel organization in multiple excitable tissues.
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spelling pubmed-22136082008-07-14 Voltage-gated Na(v) channel targeting in the heart requires an ankyrin-G–dependent cellular pathway Lowe, John S. Palygin, Oleg Bhasin, Naina Hund, Thomas J. Boyden, Penelope A. Shibata, Erwin Anderson, Mark E. Mohler, Peter J. J Cell Biol Research Articles Voltage-gated Na(v) channels are required for normal electrical activity in neurons, skeletal muscle, and cardiomyocytes. In the heart, Na(v)1.5 is the predominant Na(v) channel, and Na(v)1.5-dependent activity regulates rapid upstroke of the cardiac action potential. Na(v)1.5 activity requires precise localization at specialized cardiomyocyte membrane domains. However, the molecular mechanisms underlying Na(v) channel trafficking in the heart are unknown. In this paper, we demonstrate that ankyrin-G is required for Na(v)1.5 targeting in the heart. Cardiomyocytes with reduced ankyrin-G display reduced Na(v)1.5 expression, abnormal Na(v)1.5 membrane targeting, and reduced Na(+) channel current density. We define the structural requirements on ankyrin-G for Na(v)1.5 interactions and demonstrate that loss of Na(v)1.5 targeting is caused by the loss of direct Na(v)1.5–ankyrin-G interaction. These data are the first report of a cellular pathway required for Na(v) channel trafficking in the heart and suggest that ankyrin-G is critical for cardiac depolarization and Na(v) channel organization in multiple excitable tissues. The Rockefeller University Press 2008-01-14 /pmc/articles/PMC2213608/ /pubmed/18180363 http://dx.doi.org/10.1083/jcb.200710107 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Lowe, John S.
Palygin, Oleg
Bhasin, Naina
Hund, Thomas J.
Boyden, Penelope A.
Shibata, Erwin
Anderson, Mark E.
Mohler, Peter J.
Voltage-gated Na(v) channel targeting in the heart requires an ankyrin-G–dependent cellular pathway
title Voltage-gated Na(v) channel targeting in the heart requires an ankyrin-G–dependent cellular pathway
title_full Voltage-gated Na(v) channel targeting in the heart requires an ankyrin-G–dependent cellular pathway
title_fullStr Voltage-gated Na(v) channel targeting in the heart requires an ankyrin-G–dependent cellular pathway
title_full_unstemmed Voltage-gated Na(v) channel targeting in the heart requires an ankyrin-G–dependent cellular pathway
title_short Voltage-gated Na(v) channel targeting in the heart requires an ankyrin-G–dependent cellular pathway
title_sort voltage-gated na(v) channel targeting in the heart requires an ankyrin-g–dependent cellular pathway
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213608/
https://www.ncbi.nlm.nih.gov/pubmed/18180363
http://dx.doi.org/10.1083/jcb.200710107
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