title: Structure and function of splice variants of the cardiac voltage-gated sodium channel Na(v)1.5.
abstract: Voltage-gated sodium channels mediate the rapid upstroke of the action potential in excitable tissues. The tetrodotoxin (TTX) resistant isoform Na(v)1.5, encoded by the SCN5A gene, is the predominant isoform in the heart. This channel plays a key role for excitability of atrial and ventricular cardiomyocytes and for rapid impulse propagation through the specific conduction system. During recent years, strong evidence has been accumulated in support of the expression of several Na(v)1.5 splice variants in the heart, and in various other tissues and cell lines including brain, dorsal root ganglia, breast cancer cells and neuronal stem cell lines. This review summarizes our knowledge on the structure and putative function of nine Na(v)1.5 splice variants detected so far. Attention will be paid to the distinct biophysical properties of the four functional splice variants, to the pronounced tissue- and species-specific expression, and to the developmental regulation of Na(v)1.5 splicing. The implications of alternative splicing for SCN5A channelopathies, and for a better understanding of genotype-phenotype correlations, are discussed.
authors.affiliation: Institute of Physiology II, University Clinic, Friedrich Schiller University Jena, Kollegiengasse 9, 07743 Jena, Germany.
authors.forename: Annett
authors.initials: A
authors.lastname: Schroeter
authors.forename: Stefan
authors.initials: S
authors.lastname: Walzik
authors.forename: Steve
authors.initials: S
authors.lastname: Blechschmidt
authors.forename: Volker
authors.initials: V
authors.lastname: Haufe
authors.forename: Klaus
authors.initials: K
authors.lastname: Benndorf
authors.forename: Thomas
authors.initials: T
authors.lastname: Zimmer
mesh_terms: D000200:Action Potentials / Q000235:genetics / Q000502:physiology; D017398:Alternative Splicing; D000818:Animals; D005727:Ganglia, Spinal / Q000378:metabolism / Q000502:physiology; D056726:Genetic Association Studies; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012964:Sodium / Q000378:metabolism / Q000502:physiology; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012982:Sodium, Dietary / Q000378:metabolism; D013779:Tetrodotoxin / Q000378:metabolism / Q000502:physiology
chemical_list: D020033:Protein Isoforms; D015222:Sodium Channels; D012982:Sodium, Dietary; D013779:Tetrodotoxin; D012964:Sodium