Premium
A TTX‐Sensitive Resting Na + Permeability Contributes to the Catecholaminergic Automatic Activity in Rat Pulmonary Vein
Author(s) -
MALÉCOT CLAIRE O.,
BREDELOUX PIERRE,
FINDLAY IAN,
MAUPOIL VÉRONIQUE
Publication year - 2015
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/jce.12572
Subject(s) - ranolazine , depolarization , tetrodotoxin , medicine , quinidine , membrane potential , catecholaminergic , refractory period , pulmonary vein , biophysics , atrial fibrillation , cardiology , biology , catecholamine
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 I Na 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 I Na 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‐α 1 adrenergic effect, which contributed to its antiarrhythmic effect.