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 (I Na) 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 V max compared with LV epi and endo cells. Peak I Na density was significantly lower in epi and endo RV cells compared with epi and endo LV cells. Recovery from inactivation of I Na 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 V max and Na+ current are smaller in RV, presumably due to differential Nav1.5/β subunit expression. These results provide a potential mechanism for the right ventricular manifestation of BrS.

Highlights

  • Brugada syndrome (BrS) is an inherited disease associated with ST elevation or a broad J-wave in the right precordial leads, phase 2 reentry, polymorphic ventricular tachycardia (PVT), and sudden cardiac death in adults (Brugada and Brugada 1992)

  • The thickness of the LV wedge was always greater than the right ventricle (RV) wedge, analysis of the transmural conduction time revealed no significant difference between RV and LV wedges (13.7 Æ 2.0 msec vs. 15.0 Æ 1.6 msec, respectively; n = 8)

  • RV wall, but transmural conduction time was similar between the two chambers, suggesting less INa in the RV

Read more

Summary

Introduction

Brugada syndrome (BrS) is an inherited disease associated with ST elevation or a broad J-wave in the right precordial leads, phase 2 reentry, polymorphic ventricular tachycardia (PVT), and sudden cardiac death in adults (Brugada and Brugada 1992). Recent studies suggest a pathophysiological component in hearts from BrS patients such as increased fibrosis and fatty infiltration as well as decreased connexin proteins, in the right ventricular outflow tract (RVOT) leading to right ventricular conduction slowing. This is the basis of the depolarization hypothesis, and it a 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call