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Physiol Rep. 2018 Jul;6(14):e13787. doi: 10.14814/phy2.13787.

Interventricular differences in sodium current and its potential role in Brugada syndrome.

Author information

1
Department of Veterinary and Animal Sciences, Section for Anatomy, Biochemistry and Physiology, University of Copenhagen, Frederiksberg, Denmark.
2
Department of Experimental Cardiology, Masonic Medical Research Laboratory, Utica, New York.
3
Lankenau Institute for Medical Research, Wynnewood, Pennsylvania.

Abstract

Brugada syndrome (BrS) is an inherited disease associated with ST elevation in the right precordial leads, polymorphic ventricular tachycardia (PVT), and sudden cardiac death in adults. Mutations in the cardiac sodium channel account for a large fraction of BrS cases. BrS manifests in the right ventricle (RV), which led us to examine the biophysical and molecular properties of sodium channel in myocytes isolated from the left (LV) and right ventricle. Patch clamp was used to record sodium current (INa ) in single canine RV and LV epicardial (epi) and endocardial (endo) myocytes. Action potentials were recorded from multicellular preparations and single cells. mRNA and proteins were determined using quantitative RT-PCR and Western blot. Although LV wedge preparations were thicker than RV wedges, transmural ECG recordings showed no difference in the width of the QRS complex or transmural conduction time. Action potential characteristics showed RV epi and endo had a lower Vmax compared with LV epi and endo cells. Peak INa density was significantly lower in epi and endo RV cells compared with epi and endo LV cells. Recovery from inactivation of INa in RV cells was slightly faster and half maximal steady-state inactivation was more positive. β2 and β4 mRNA was detected at very low levels in both ventricles, which was confirmed at the protein level. Our observations demonstrate that Vmax and Na+ current are smaller in RV, presumably due to differential Nav 1.5/β subunit expression. These results provide a potential mechanism for the right ventricular manifestation of BrS.

KEYWORDS:

Action Potentials; left ventricle; patch clamp; right ventricle; sodium current

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