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Control hormonal de las corrientes de la fase 1 del potencial de acción cardiaco en el síndrome de Brugada;
Hormonal Control of Cardiac Action Potential Phase 1 Currents in the Brugada Syndrome

Creators:Argenziano, Mariana, Tiscornia, Gisela, Moretta, Rosalía, Amorena, Carlos E., García Gras, Eduardo; Centro de Estudios en Salud y Medio Ambiente (CESyMA), Escuela de Ciencia y Tecnología (ECyT), Universidad Nacional de San Martín (UNSAM.
CONICET Buenos Aires Argentina

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Descripción

El síndrome de Brugada es una canalopatía hereditaria con un patrón de transmisión autosómico dominante que presenta una marcado sesgo de genero en la expresión del fenotipo, con una razón hombre:mujer de 9:1. Un modelo celular de la enfermedad propone una distribución heterogénea de la amplitud de la fase 1 del potencial de acción ventrícular como la base para el desarrollo del sustrato arritmogénico. Nosotros hemos investigado el papel de los andrógenos en la regulación de la fase 1 del potencial de acción en corazones de ratas. El tratamiento de células HL-1 con di-hidro-testosterona produjo un aumento en la expresión de Kv4.3 y NCX. Evaluamos este efecto en ratas tratadas con Testosterona y Finasteride. La expresión de ambos genes fue disminuída por el Finasteride, mientras que la Testosterona aumentó el nivel de ARNm de NCX. Estudiamos los potenciales de acción en el corazón de rata aislado y perfundido en respuesta a un protocolo de arritmia luego de ser tratados con Terfenadina y Pinacidil. La Testosterona produjo un acortamiento del  APD90 y el TTP, lo cual en modelos del SBr se correlaciona con un aumento de la arritmogenicidad. En nuestro modelo, este fenómeno fue observado como un incremento en los potenciales de acción ventriculares ectópicos, esporádicos y sostenidos. La frecuencia de aparición de potenciales de acción ectópicos que se indujo con Terfenadina y Pinacidil en el grupo Control fue reducida en un orden de magnitud por el tratamiento con Finasteride.

Introduction: The Brugada syndrome is an inherited channelopathy with autosomal dominant genotype transmission patternpresenting marked gender bias in phenotype expression, with a male to female ratio of 9:1. A cellular model of the diseasesuggests a heterogeneous distribution in the phase 1 amplitude of the ventricular action potential as the origin for the developmentof the arrhythmogenic substrate.Objective: The aim of this study was to investigate the role of androgens on the cardiac action potential phase 1 regulationand 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 chainreaction (PCR). For the electrophysiological studies, an experimental model of the Brugada syndrome was reproduced in aLangendorff 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 thesodium/calcium exchanger (NCX). This effect was assessed in rats treated with testosterone and finasteride. The expressionof both genes decreased with finasteride, where as testosterone increased NCX messenger ribonucleic acid (mRNA) level.Testosterone produced action potential shortening at 90% repolarization (APD90) and decreased time to peak (TTP), whichin Brugada syndrome models correlate with increased arrhythmogenesis. In our model, this phenomenon was observed bothas an increase of sporadic and sustained ectopic ventricular action potentials. The frequency of ectopic action potentials inducedwith 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.

Metadatos destacados

Colecciones
Argentine Journal of Cardiology

Editor

Sociedad Argentina de Cardiología

Fuente

Revista Argentina de Cardiología; Vol 82, No 4 (2014); 310-315, Argentine Journal of Cardiology; Vol 82, No 4 (2014); 310-315

Citación

Argenziano, Mariana et al., “Control hormonal de las corrientes de la fase 1 del potencial de acción cardiaco en el síndrome de Brugada,” Archivo PPCT, consulta 2 de abril de 2026, http://archivoppct.caicyt.gov.ar/items/show/8509.

Dublin Core

Autor

Argenziano, Mariana
Tiscornia, Gisela
Moretta, Rosalía
Amorena, Carlos E.
García Gras, Eduardo; Centro de Estudios en Salud y Medio Ambiente (CESyMA), Escuela de Ciencia y Tecnología (ECyT), Universidad Nacional de San Martín (UNSAM.
CONICET Buenos Aires Argentina

Fuente

Revista Argentina de Cardiología; Vol 82, No 4 (2014); 310-315
Argentine Journal of Cardiology; Vol 82, No 4 (2014); 310-315

Editor

Sociedad Argentina de Cardiología

Fecha

2014-08-15

Derechos

Los que firman al pié, certificamos que tenemos total responsabilidad por la conducción de este estudio y por el diseño y la interpretación de los datos. Nosotros escribimos el manuscrito y somos responsables por la decisión acerca del mismo. Cada uno de nosotros cumple la definición de autor como se afirma en el Comité Internacional de Editores de Revistas Médicas (International Committee of Medical Journal Editors, ver www.icmje.org). Nosotros hemos visto y aprobado el manuscrito final. Ni el artículo, ni ninguna parte esencial del mismo, incluido las tablas y las figuras, será publicado o admitido para arbitrar a otra parte antes de aparecer en la Revista.También notificamos haber leído la sección “conflicto de intereses”, y revelaríamos cualquiera que existiera. Dejamos constancia que si nuestro artículo se publicara en la RAC, cederíamos los derechos (copyright) a la Revista.Los documentos publicados en esta revista están bajo la licencia Creative Commons Atribución-NoComercial-Compartir-Igual 2.5 Argentina.
Those signing below certify that we have full responsibility for the conduction of this study and for the design and interpretation of the information. We wrote the manuscript and are responsible for its decision. Each of us fulfills the definition of authorship as stated by the International Committee of Medical Journal Editors ( www.icmje.org). We have signed and approved the final manuscript. Neither the manuscript, nor any essential part thereof, including tables and figures, will be published or accepted for refereeing elsewhere before being published in the Journal. We have also read the "Conflict of Interest" section and would disclose any existing. We state that if our manuscript is published in the RAC, we shall transfer the copyright to the Journal.

Idioma

eng
spa

Tipo

info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion