Inherited Cardiac Diseases Caused by Mutations in the Nav1.5 Sodium Channel

Authors

  • JACOB TFELT-HANSEN M.D., Ph.D.,

    1. The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Copenhagen, Denmark
    2. Laboratory of Molecular Cardiology, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Denmark
    Search for more papers by this author
  • BO GREGERS WINKEL M.D.,

    1. The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Copenhagen, Denmark
    2. Laboratory of Molecular Cardiology, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Denmark
    Search for more papers by this author
  • MORTEN GRUNNET Ph.D.,

    1. The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Copenhagen, Denmark
    2. Department of Medical Physiology, Panum Institute, University of Copenhagen, Copenhagen, Denmark
    3. NeuroSearch A/S, Ballerup, Denmark
    Search for more papers by this author
  • THOMAS JESPERSEN Ph.D.

    1. The Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Copenhagen, Denmark
    2. Department of Medical Physiology, Panum Institute, University of Copenhagen, Copenhagen, Denmark
    Search for more papers by this author

  • This work was supported by the Danish National Research Foundation to Drs. Tfelt-Hansen, Winkel, Jespersen, and Grunnet; Meyers Family Foundation to Drs. Tfelt-Hansen and Winkel; The Danish Heart Foundation to Dr. Winkel; The Danish Medical Research Council, The Novo Nordisk Foundation, and the Aase and Einer Danielsen Foundation to Dr. Grunnet; and the Lundbeck Foundation to Dr. Jespersen.

  • The authors have declared no conflicts of interest.

  • Section Editor: Silvia G. Priori, M.D., Ph.D

Address for correspondence: Jacob Tfelt-Hansen, M.D. Ph.D., Laboratory of Molecular Cardiology, Department of Cardiology, section 9312, Copenhagen University Hospital, Rigshospitalet, Juliane Mariesvej 20, DK 2100 Copenhagen, Denmark. Fax: +45 35456500; E-mail: tfelt@dadlnet.dk

Abstract

Cardiac Diseases Caused by SCN5A Mutations.  A prerequisite for a normal cardiac function is a proper generation and propagation of electrical impulses. Contraction of the heart is obtained through a delicate matched transmission of the electrical impulses. A pivotal element of the impulse propagation is the depolarizing sodium current, responsible for the initial depolarization of the cardiomyocytes. Recent research has shown that mutations in the SCN5A gene, encoding the cardiac sodium channel Nav1.5, are associated with both rare forms of ventricular arrhythmia, as well as the most frequent form of arrhythmia, atrial fibrillation (AF). In this comprehensive review, we describe the functional role of Nav1.5 and its associated proteins in propagation and depolarization both in a normal- and in a pathophysiological setting. Furthermore, several of the arrhythmogenic diseases, such as long-QT syndrome, Brugada syndrome, and AF, reported to be associated with mutations in SCN5A, are thoroughly described. (J Cardiovasc Electrophysiol, Vol. 21, pp. 107–115, January 2010)

Ancillary