Phase 1 repolarization rate defines Ca<SUP>2+</SUP> dynamics and contractility on intact mouse hearts

In the heart, Ca2+ influx through L-type Ca2+ channels triggers Ca2+ release from the sarcoplasmic reticulum. In most mammals, this influx occurs during the ventricular action potential (AP) plateau phase 2. However, in murine models, the influx through L-type Ca2+ channels happens in early repolari...

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Autores principales: López Alarcón, María Micaela, Rodríguez de Yurre, Ainhoa, Felice, Juan Ignacio, Medei, Emiliano, Escobar, Ariel L.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2019
Materias:
Ciencias Médicas
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/107350
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6571993&blobtype=pdf
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SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-107350
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
spellingShingle Ciencias Médicas
López Alarcón, María Micaela
Rodríguez de Yurre, Ainhoa
Felice, Juan Ignacio
Medei, Emiliano
Escobar, Ariel L.
Phase 1 repolarization rate defines Ca<SUP>2+</SUP> dynamics and contractility on intact mouse hearts
topic_facet Ciencias Médicas
description In the heart, Ca2+ influx through L-type Ca2+ channels triggers Ca2+ release from the sarcoplasmic reticulum. In most mammals, this influx occurs during the ventricular action potential (AP) plateau phase 2. However, in murine models, the influx through L-type Ca2+ channels happens in early repolarizing phase 1. The aim of this work is to assess if changes in the open probability of 4-aminopyridine (4-AP)–sensitive Kv channels defining the outward K+ current during phase 1 can modulate Ca2+ currents, Ca2+ transients, and systolic pressure during the cardiac cycle in intact perfused beating hearts. Pulsed local-field fluorescence microscopy and loose-patch photolysis were used to test the hypothesis that a decrease in a transient K+ current (Ito) will enhance Ca2+ influx and promote a larger Ca2+ transient. Simultaneous recordings of Ca2+ transients and APs by pulsed local-field fluorescence microscopy and loose-patch photolysis showed that a reduction in the phase 1 repolarization rate increases the amplitude of Ca2+ transients due to an increase in Ca2+ influx through L-type Ca2+ channels. Moreover, 4-AP induced an increase in the time required for AP to reach 30% repolarization, and the amplitude of Ca2+ transients was larger in epicardium than endocardium. On the other hand, the activation of Ito with NS5806 resulted in a reduction of Ca2+ current amplitude that led to a reduction of the amplitude of Ca2+ transients. Finally, the 4-AP effect on AP phase 1 was significantly smaller when the L-type Ca2+ current was partially blocked with nifedipine, indicating that the phase 1 rate of repolarization is defined by the competition between an outward K+ current and an inward Ca2+ current.
format Articulo
Articulo
author López Alarcón, María Micaela
Rodríguez de Yurre, Ainhoa
Felice, Juan Ignacio
Medei, Emiliano
Escobar, Ariel L.
author_facet López Alarcón, María Micaela
Rodríguez de Yurre, Ainhoa
Felice, Juan Ignacio
Medei, Emiliano
Escobar, Ariel L.
author_sort López Alarcón, María Micaela
title Phase 1 repolarization rate defines Ca<SUP>2+</SUP> dynamics and contractility on intact mouse hearts
title_short Phase 1 repolarization rate defines Ca<SUP>2+</SUP> dynamics and contractility on intact mouse hearts
title_full Phase 1 repolarization rate defines Ca<SUP>2+</SUP> dynamics and contractility on intact mouse hearts
title_fullStr Phase 1 repolarization rate defines Ca<SUP>2+</SUP> dynamics and contractility on intact mouse hearts
title_full_unstemmed Phase 1 repolarization rate defines Ca<SUP>2+</SUP> dynamics and contractility on intact mouse hearts
title_sort phase 1 repolarization rate defines ca<sup>2+</sup> dynamics and contractility on intact mouse hearts
publishDate 2019
url http://sedici.unlp.edu.ar/handle/10915/107350
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6571993&blobtype=pdf
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bdutipo_str Repositorios
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