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Title

A TTX-Sensitive Resting Na Permeability Contributes to the Catecholaminergic Automatic Activity in Rat Pulmonary Vein.

Authors

MALÉCOT, CLAIRE O.; BREDELOUX, PIERRE; FINDLAY, IAN; MAUPOIL, VÉRONIQUE

Abstract

Na Channels and Automatic Activity in Rat PV 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.

Subjects

ANALYSIS of variance; ANIMAL experimentation; ATRIAL fibrillation; BIOLOGICAL transport; CATECHOLAMINES; ELECTROPHYSIOLOGY; FISHER exact test; MARINE toxins; MEMBRANE proteins; NORADRENALINE; PIPERAZINE; PULMONARY veins; QUINIDINE; RATS; RESEARCH funding; SODIUM; STATISTICS; T-test (Statistics); DATA analysis; DATA analysis software; DESCRIPTIVE statistics; LEFT heart atrium; MANN Whitney U Test

Publication

Journal of Cardiovascular Electrophysiology, 2015, Vol 26, Issue 3, p311

ISSN

1045-3873

Publication type

Academic Journal

DOI

10.1111/jce.12572

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