Abstract

ARGENZIANO, Mariana et al. Hormonal Control of Cardiac Action Potential Phase 1 Currents in the Brugada Syndrome. Rev. argent. cardiol. [online]. 2014, vol.82, n.4, pp.310-315. ISSN 1850-3748.

Introduction The Brugada syndrome is an inherited channelopathy with autosomal dominant genotype transmission pattern presenting marked gender bias in phenotype expression, with a male to female ratio of 9:1. A cellular model of the disease suggests a heterogeneous distribution in the phase 1 amplitude of the ventricular action potential as the origin for the development of the arrhythmogenic substrate. Objective The aim of this study was to investigate the role of androgens on the cardiac action potential phase 1 regulation and its electrophysiological consequences in an experimental murine model of Brugada syndrome. Methods Androgen control of gene expression was studied in HL-1 cells and rat hearts using real time polymerase chain reaction (PCR). For the electrophysiological studies, an experimental model of the Brugada syndrome was reproduced in a Langendorff system using Tyrode solution supplemented with pinacidil and terfenadine. Results Treatment of HL-1 cells with di-hydro-testosterone increased the expression of the Kv4.3 potassium channel and the sodium/calcium exchanger (NCX). This effect was assessed in rats treated with testosterone and finasteride. The expression of both genes decreased with finasteride, whereas testosterone increased NCX messenger ribonucleic acid (mRNA) level. Testosterone produced action potential shortening at 90% repolarization (APD90) and decreased time to peak (TTP), which in Brugada syndrome models correlate with increased arrhythmogenesis. In our model, this phenomenon was observed both as an increase of sporadic and sustained ectopic ventricular action potentials. The frequency of ectopic action potentials induced with terfenadine and pinacidil in the control group was reduced by an order of magnitude with finasteride treatment. Conclusions Androgens control the expression of key components of the cardiac action potential resulting in increased arrhythmogenesis. Finasteride treatment reverses these effects.

Keywords : Brugada Syndrome; Cardíac Arrhythmías; Androgens; Finasteride.

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