title: Prolongation of action potential duration and QT interval during epilepsy linked to increased contribution of neuronal sodium channels to cardiac late Na+ current: potential mechanism for sudden death in epilepsy.
abstract: BACKGROUND
  Arrhythmias associated with QT prolongation on the ECG often lead to sudden unexpected death in epilepsy. The mechanism causing a prolongation of the QT interval during epilepsy remains unknown. Based on observations showing an upregulation of neuronal sodium channels in the brain during epilepsy, we tested the hypothesis that a similar phenomenon occurs in the heart and contributes to QT prolongation by altering cardiac sodium current properties (INa).
  
  
  RESULTS
  We used the patch clamp technique to assess the effects of epilepsy on the cardiac action potential and INa in rat ventricular myocytes. Consistent with QT prolongation, epileptic rats had longer ventricular action potential durations attributable to a sustained component of INa (INaL). The increase in INaL was because of a larger contribution of neuronal Na channels characterized by their high sensitivity to tetrodotoxin. As in the brain, epilepsy was associated with an enhanced expression of the neuronal isoform NaV1.1 in cardiomyocyte. Epilepsy was also associated with a lower INa activation threshold resulting in increased cell excitability.
  
  
  CONCLUSIONS
  This is the first study correlating increased expression of neuronal sodium channels within the heart to epilepsy-related cardiac arrhythmias. This represents a new paradigm in our understanding of cardiac complications related to epilepsy.
authors.affiliation: From the Département de Pharmacologie et Physiologie, Université de Sherbrooke, Sherbrooke, Canada (M.B., N.M., M.L.-B., R.K.G., R.D.); and Department of Pediatrics, Centre de Recherche du CHU Sainte Justine, Université de Montréal, Montréal, Quebec, Canada (S.D., J.G., N.T.S., L.C.).
authors.forename: Michael
authors.initials: M
authors.lastname: Biet
authors.affiliation: From the Département de Pharmacologie et Physiologie, Université de Sherbrooke, Sherbrooke, Canada (M.B., N.M., M.L.-B., R.K.G., R.D.); and Department of Pediatrics, Centre de Recherche du CHU Sainte Justine, Université de Montréal, Montréal, Quebec, Canada (S.D., J.G., N.T.S., L.C.).
authors.forename: Nathalie
authors.initials: N
authors.lastname: Morin
authors.affiliation: From the Département de Pharmacologie et Physiologie, Université de Sherbrooke, Sherbrooke, Canada (M.B., N.M., M.L.-B., R.K.G., R.D.); and Department of Pediatrics, Centre de Recherche du CHU Sainte Justine, Université de Montréal, Montréal, Quebec, Canada (S.D., J.G., N.T.S., L.C.).
authors.forename: Melissa
authors.initials: M
authors.lastname: Lessard-Beaudoin
authors.affiliation: From the Département de Pharmacologie et Physiologie, Université de Sherbrooke, Sherbrooke, Canada (M.B., N.M., M.L.-B., R.K.G., R.D.); and Department of Pediatrics, Centre de Recherche du CHU Sainte Justine, Université de Montréal, Montréal, Quebec, Canada (S.D., J.G., N.T.S., L.C.).
authors.forename: Rona K
authors.initials: RK
authors.lastname: Graham
authors.affiliation: From the Département de Pharmacologie et Physiologie, Université de Sherbrooke, Sherbrooke, Canada (M.B., N.M., M.L.-B., R.K.G., R.D.); and Department of Pediatrics, Centre de Recherche du CHU Sainte Justine, Université de Montréal, Montréal, Quebec, Canada (S.D., J.G., N.T.S., L.C.).
authors.forename: Sandra
authors.initials: S
authors.lastname: Duss
authors.affiliation: From the Département de Pharmacologie et Physiologie, Université de Sherbrooke, Sherbrooke, Canada (M.B., N.M., M.L.-B., R.K.G., R.D.); and Department of Pediatrics, Centre de Recherche du CHU Sainte Justine, Université de Montréal, Montréal, Quebec, Canada (S.D., J.G., N.T.S., L.C.).
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gagné
authors.affiliation: From the Département de Pharmacologie et Physiologie, Université de Sherbrooke, Sherbrooke, Canada (M.B., N.M., M.L.-B., R.K.G., R.D.); and Department of Pediatrics, Centre de Recherche du CHU Sainte Justine, Université de Montréal, Montréal, Quebec, Canada (S.D., J.G., N.T.S., L.C.).
authors.forename: Nathalie T
authors.initials: NT
authors.lastname: Sanon
authors.affiliation: From the Département de Pharmacologie et Physiologie, Université de Sherbrooke, Sherbrooke, Canada (M.B., N.M., M.L.-B., R.K.G., R.D.); and Department of Pediatrics, Centre de Recherche du CHU Sainte Justine, Université de Montréal, Montréal, Quebec, Canada (S.D., J.G., N.T.S., L.C.).
authors.forename: Lionel
authors.initials: L
authors.lastname: Carmant
authors.affiliation: From the Département de Pharmacologie et Physiologie, Université de Sherbrooke, Sherbrooke, Canada (M.B., N.M., M.L.-B., R.K.G., R.D.); and Department of Pediatrics, Centre de Recherche du CHU Sainte Justine, Université de Montréal, Montréal, Quebec, Canada (S.D., J.G., N.T.S., L.C.). robert.dumaine@usherbrooke.ca.
authors.forename: Robert
authors.initials: R
authors.lastname: Dumaine
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D004247:DNA / Q000235:genetics*; D003645:Death, Sudden / Q000209:etiology*; D004827:Epilepsy / Q000150:complications / Q000378:metabolism* / Q000401:mortality; D005786:Gene Expression Regulation; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism*; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000096:biosynthesis / Q000235:genetics*; D018408:Patch-Clamp Techniques; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; D004247:DNA
keywords: action potentials; arrhythmias; cardiac; death; electrophysiology; epilepsy; sodium channels; sudden