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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.

Publication ,  Journal Article
Mohler, PJ; Rivolta, I; Napolitano, C; LeMaillet, G; Lambert, S; Priori, SG; Bennett, V
Published in: Proc Natl Acad Sci U S A
December 14, 2004

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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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

December 14, 2004

Volume

101

Issue

50

Start / End Page

17533 / 17538

Location

United States

Related Subject Headings

  • Syndrome
  • Sodium Channels
  • Protein Binding
  • NAV1.5 Voltage-Gated Sodium Channel
  • Myocytes, Cardiac
  • Myocardium
  • Mutation, Missense
  • Muscle Proteins
  • Molecular Sequence Data
  • Mice
 

Citation

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Mohler, P. J., Rivolta, I., Napolitano, C., LeMaillet, G., Lambert, S., Priori, S. G., & Bennett, V. (2004). Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes. Proc Natl Acad Sci U S A, 101(50), 17533–17538. https://doi.org/10.1073/pnas.0403711101
Mohler, Peter J., Ilaria Rivolta, Carlo Napolitano, Guy LeMaillet, Stephen Lambert, Silvia G. Priori, and Vann Bennett. “Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes.Proc Natl Acad Sci U S A 101, no. 50 (December 14, 2004): 17533–38. https://doi.org/10.1073/pnas.0403711101.
Mohler PJ, Rivolta I, Napolitano C, LeMaillet G, Lambert S, Priori SG, et al. Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes. Proc Natl Acad Sci U S A. 2004 Dec 14;101(50):17533–8.
Mohler, Peter J., et al. “Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes.Proc Natl Acad Sci U S A, vol. 101, no. 50, Dec. 2004, pp. 17533–38. Pubmed, doi:10.1073/pnas.0403711101.
Mohler PJ, Rivolta I, Napolitano C, LeMaillet G, Lambert S, Priori SG, Bennett V. Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes. Proc Natl Acad Sci U S A. 2004 Dec 14;101(50):17533–17538.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

December 14, 2004

Volume

101

Issue

50

Start / End Page

17533 / 17538

Location

United States

Related Subject Headings

  • Syndrome
  • Sodium Channels
  • Protein Binding
  • NAV1.5 Voltage-Gated Sodium Channel
  • Myocytes, Cardiac
  • Myocardium
  • Mutation, Missense
  • Muscle Proteins
  • Molecular Sequence Data
  • Mice