Voltage-gated Nav channel targeting in the heart requires an ankyrin-G dependent cellular pathway.

Voltage-gated Nav channel targeting in the heart requires an ankyrin-G dependent cellular pathway. Research Abstract Details 

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Voltage-gated Nav channel targeting in the heart requires an ankyrin-G dependent cellular pathway. Abstract Text:

John S Lowe,Oleg Palygin,Naina Bhasin,Thomas J Hund,Penelope A Boyden,Erwin Shibata,Mark E Anderson,Peter J Mohler,John S Lowe,Oleg Palygin,Naina Bhasin,Thomas J Hund,Penelope A Boyden,Erwin Shibata,Mark E Anderson,Peter J Mohler,

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.

Voltage-gated Nav channel targeting in the heart requires an ankyrin-G dependent cellular pathway. Publishing Authors By Initials

JS Lowe,O Palygin,N Bhasin,TJ Hund,PA Boyden,E Shibata,ME Anderson,PJ Mohler,JS Lowe,O Palygin,N Bhasin,TJ Hund,PA Boyden,E Shibata,ME Anderson,PJ Mohler,

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Voltage-gated Nav channel targeting in the heart requires an ankyrin-G dependent cellular pathway. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of cell biology

VOLUME: 180

Page Numbers: 173-86

Journal Abbreviation: J. Cell Biol.

ISSN: 1540-8140

DAY: 7

MONTH: 01

YEAR: 2008

Voltage-gated Nav channel targeting in the heart requires an ankyrin-G dependent cellular pathway. Information

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LANGUAGE: eng

NlmUniqueID: 375356

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Grant and Affiliation Information for Voltage-gated Nav channel targeting in the heart requires an ankyrin-G dependent cellular pathway.

AFFILIATION: Department of Internal Medicine, Division of Cardiology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL70250

ACRONYM: HL

MEDLINETA: J Cell Biol

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