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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...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2008
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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. |
format | Text |
id | pubmed-2213608 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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