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

Area of Science:

• Cardiovascular Physiology
• Molecular Cardiology
• Electrophysiology

Background:

• Brugada syndrome (BrS) is an inherited cardiac disease linked to sudden cardiac death.
• Mutations in cardiac sodium channels are a common cause of BrS.
• BrS clinically manifests in the right ventricle, but the underlying cellular mechanisms remain unclear.

Purpose of the Study:

• To investigate the biophysical and molecular properties of sodium channels in canine right (RV) and left ventricular (LV) myocytes.
• To explore potential differences that could explain the right ventricular manifestation of Brugada syndrome.

Main Methods:

• Patch-clamp electrophysiology to record sodium current (I_Na) and action potentials in RV and LV epicardial and endocardial myocytes.
• Quantitative RT-PCR and Western blot to assess mRNA and protein expression of sodium channel subunits.

Main Results:

• RV myocytes exhibited lower maximal upstroke velocity (V_max) and peak I_Na density compared to LV myocytes.
• Action potential characteristics differed, with RV cells showing faster recovery from inactivation and a more positive half-maximal steady-state inactivation.
• Low levels of β2 and β4 mRNA and protein for sodium channel subunits were detected in both ventricles.

Conclusions:

• Reduced sodium current and altered electrophysiological properties in RV myocytes may underlie the right ventricular manifestation of Brugada syndrome.
• Differential expression of Na_v1.5/β subunits is a potential mechanism contributing to these observed differences.