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Phase 1 repolarization rate defines Ca(2+) dynamics and contractility on intact mouse hearts

In the heart, Ca(2+) influx through L-type Ca(2+) channels triggers Ca(2+) 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 Ca(2+) channels happens in early...

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Autores principales: López Alarcón, María Micaela, Rodríguez de Yurre, Ainhoa, Felice, Juan Ignacio, Medei, Emiliano, Escobar, Ariel L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571993/
https://www.ncbi.nlm.nih.gov/pubmed/31000581
http://dx.doi.org/10.1085/jgp.201812269
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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
collection PubMed
description In the heart, Ca(2+) influx through L-type Ca(2+) channels triggers Ca(2+) 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 Ca(2+) 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 Ca(2+) currents, Ca(2+) 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 (I(to)) will enhance Ca(2+) influx and promote a larger Ca(2+) transient. Simultaneous recordings of Ca(2+) 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 Ca(2+) transients due to an increase in Ca(2+) influx through L-type Ca(2+) channels. Moreover, 4-AP induced an increase in the time required for AP to reach 30% repolarization, and the amplitude of Ca(2+) transients was larger in epicardium than endocardium. On the other hand, the activation of I(to) with NS5806 resulted in a reduction of Ca(2+) current amplitude that led to a reduction of the amplitude of Ca(2+) transients. Finally, the 4-AP effect on AP phase 1 was significantly smaller when the L-type Ca(2+) 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 Ca(2+) current.
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spelling pubmed-65719932019-12-04 Phase 1 repolarization rate defines Ca(2+) dynamics and contractility on intact mouse hearts López Alarcón, María Micaela Rodríguez de Yurre, Ainhoa Felice, Juan Ignacio Medei, Emiliano Escobar, Ariel L. J Gen Physiol Research Articles In the heart, Ca(2+) influx through L-type Ca(2+) channels triggers Ca(2+) 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 Ca(2+) 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 Ca(2+) currents, Ca(2+) 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 (I(to)) will enhance Ca(2+) influx and promote a larger Ca(2+) transient. Simultaneous recordings of Ca(2+) 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 Ca(2+) transients due to an increase in Ca(2+) influx through L-type Ca(2+) channels. Moreover, 4-AP induced an increase in the time required for AP to reach 30% repolarization, and the amplitude of Ca(2+) transients was larger in epicardium than endocardium. On the other hand, the activation of I(to) with NS5806 resulted in a reduction of Ca(2+) current amplitude that led to a reduction of the amplitude of Ca(2+) transients. Finally, the 4-AP effect on AP phase 1 was significantly smaller when the L-type Ca(2+) 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 Ca(2+) current. Rockefeller University Press 2019-06-03 2019-04-18 /pmc/articles/PMC6571993/ /pubmed/31000581 http://dx.doi.org/10.1085/jgp.201812269 Text en © 2019 López-Alarcón et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
López Alarcón, María Micaela
Rodríguez de Yurre, Ainhoa
Felice, Juan Ignacio
Medei, Emiliano
Escobar, Ariel L.
Phase 1 repolarization rate defines Ca(2+) dynamics and contractility on intact mouse hearts
title Phase 1 repolarization rate defines Ca(2+) dynamics and contractility on intact mouse hearts
title_full Phase 1 repolarization rate defines Ca(2+) dynamics and contractility on intact mouse hearts
title_fullStr Phase 1 repolarization rate defines Ca(2+) dynamics and contractility on intact mouse hearts
title_full_unstemmed Phase 1 repolarization rate defines Ca(2+) dynamics and contractility on intact mouse hearts
title_short Phase 1 repolarization rate defines Ca(2+) dynamics and contractility on intact mouse hearts
title_sort phase 1 repolarization rate defines ca(2+) dynamics and contractility on intact mouse hearts
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571993/
https://www.ncbi.nlm.nih.gov/pubmed/31000581
http://dx.doi.org/10.1085/jgp.201812269
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