title: A TTX-sensitive resting Na+ permeability contributes to the catecholaminergic automatic activity in rat pulmonary vein.
abstract: BACKGROUND
  Ectopic activity arising from pulmonary veins (PV) plays a prominent role in the onset of atrial fibrillation in humans. Rat PV cardiac muscle cells have a lower resting membrane potential (RMP) than the left atria (LA) and presents in the presence of norepinephrine an automatic activity, which occurs in bursts. This study investigated the role of Na channels upon the RMP and the catecholaminergic automatic activity (CAA) in PV cardiac muscle.
  
  
  RESULTS
  RMP and CAA experiments were performed in male Wistar rat PV. Whole-cell INa was recorded in isolated PV and LA cardiomyocytes. PV has a higher tetrodotoxin (TTX)-sensitive basal Na(+) permeability than the LA, due to a ∼ 5 mV more negative Na window current in the former tissue. TTX, quinidine, and ranolazine (1 to 10 μM each) decreased CAA incidence and arrhythmias by increasing burst intervals because of a reduction of the slope of slow depolarization between bursts. TTX and ranolazine also reduced burst duration. At 1 Hz, 10 μM quinidine, ranolazine, and TTX inhibited peak INa by 33%, 28%, and 98%, respectively. Each reduced the Na window current. There was no evidence for a TTX- or ranolazine-sensitive late Na current.
  
  
  CONCLUSIONS
  Na channels confer a TTX-sensitive basal Na(+) permeability to rat PV cardiac muscle cells and contribute to the slope of slow depolarization between bursts of CAA. Na channel blockers act mostly via reduction of the Na window current. Ranolazine also has an anti-α1 adrenergic effect, which contributed to its antiarrhythmic effect.
authors.affiliation: CNRS ERL 7368, Laboratoire Signalisation et Transports Ioniques Membranaires, Universités de Poitiers et François-Rabelais de Tours, France; Groupe Physiologie des Cellules Cardiaques et Vasculaires, Université François-Rabelais, Tours, France.
authors.forename: Claire O
authors.initials: CO
authors.lastname: Malécot
authors.forename: Pierre
authors.initials: P
authors.lastname: Bredeloux
authors.forename: Ian
authors.initials: I
authors.lastname: Findlay
authors.forename: Véronique
authors.initials: V
authors.lastname: Maupoil
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009924:Organ Culture Techniques; D011667:Pulmonary Veins / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology*
chemical_list: D002395:Catecholamines; D015222:Sodium Channels; D013779:Tetrodotoxin; D012964:Sodium
keywords: TTX; atrial fibrillation; isolated cardiomyocytes; quinidine; ranolazine; sodium channels