Claire O Malécot1, Pierre Bredeloux, Ian Findlay, Véronique Maupoil. 1. 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.
Abstract
INTRODUCTION: 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. METHODS AND 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. CONCLUSION: 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.
INTRODUCTION: 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. METHODS AND 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. CONCLUSION: 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: Ksenia B Pustovit; Daria V Samoilova; Denis V Abramochkin; Tatiana S Filatova; Vladislav S Kuzmin Journal: J Physiol Biochem Date: 2022-07-08 Impact factor: 4.158
Authors: Saagar Mahida; Frederic Sacher; Nicolas Derval; Benjamin Berte; Seigo Yamashita; Darren Hooks; Arnaud Denis; Sana Amraoui; Meleze Hocini; Michel Haissaguerre; Pierre Jais Journal: Arrhythm Electrophysiol Rev Date: 2015-05-30
Authors: C Pasqualin; A Yu; C O Malécot; F Gannier; C Cognard; D Godin-Ribuot; J Morand; P Bredeloux; V Maupoil Journal: Sci Rep Date: 2018-02-19 Impact factor: 4.379