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Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes.

Authors: Mohler, PJ  Rivolta, I  Napolitano, C  LeMaillet, G  Lambert, S  Priori, SG  Bennett, V 
Citation: Mohler PJ, etal., Proc Natl Acad Sci U S A. 2004 Dec 14;101(50):17533-8. Epub 2004 Dec 3.
Pubmed: (View Article at PubMed) PMID:15579534
DOI: Full-text: DOI:10.1073/pnas.0403711101

We identify a human mutation (E1053K) in the ankyrin-binding motif of Na(v)1.5 that is associated with Brugada syndrome, a fatal cardiac arrhythmia caused by altered function of Na(v)1.5. The E1053K mutation abolishes binding of Na(v)1.5 to ankyrin-G, and also prevents accumulation of Na(v)1.5 at cell surface sites in ventricular cardiomyocytes. Ankyrin-G and Na(v)1.5 are both localized at intercalated disc and T-tubule membranes in cardiomyocytes, and Na(v)1.5 coimmunoprecipitates with 190-kDa ankyrin-G from detergent-soluble lysates from rat heart. These data suggest that Na(v)1.5 associates with ankyrin-G and that ankyrin-G is required for Na(v)1.5 localization at excitable membranes in cardiomyocytes. Together with previous work in neurons, these results in cardiomyocytes suggest that ankyrin-G participates in a common pathway for localization of voltage-gated Na(v) channels at sites of function in multiple excitable cell types.


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CRRD Object Information
CRRD ID: 6484228
Created: 2012-06-15
Species: All species
Last Modified: 2012-06-15
Status: ACTIVE


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