Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

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

Authors: Lowe, JS  Palygin, O  Bhasin, N  Hund, TJ  Boyden, PA  Shibata, E  Anderson, ME  Mohler, PJ 
Citation: Lowe JS, etal., J Cell Biol. 2008 Jan 14;180(1):173-86. Epub 2008 Jan 7.
Pubmed: (View Article at PubMed) PMID:18180363
DOI: Full-text: DOI:10.1083/jcb.200710107

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.

Annotation

Gene Ontology Annotations
Objects Annotated

Additional Information

 
CRRD Object Information
CRRD ID: 6767295
Created: 2012-07-06
Species: All species
Last Modified: 2012-07-06
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.