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Modulation by Endothelin-1 of Spontaneous Activity and Membrane Currents of Atrioventricular Node Myocytes from the Rabbit Heart
BACKGROUND: The atrioventricular node (AVN) is a key component of the cardiac pacemaker-conduction system. Although it is known that receptors for the peptide hormone endothelin-1 (ET-1) are expressed in the AVN, there is very little information available on the modulatory effects of ET-1 on AVN ele...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315568/ https://www.ncbi.nlm.nih.gov/pubmed/22479400 http://dx.doi.org/10.1371/journal.pone.0033448 |
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author | Choisy, Stéphanie C. Cheng, Hongwei Smith, Godfrey L. James, Andrew F. Hancox, Jules C. |
author_facet | Choisy, Stéphanie C. Cheng, Hongwei Smith, Godfrey L. James, Andrew F. Hancox, Jules C. |
author_sort | Choisy, Stéphanie C. |
collection | PubMed |
description | BACKGROUND: The atrioventricular node (AVN) is a key component of the cardiac pacemaker-conduction system. Although it is known that receptors for the peptide hormone endothelin-1 (ET-1) are expressed in the AVN, there is very little information available on the modulatory effects of ET-1 on AVN electrophysiology. This study characterises for the first time acute modulatory effects of ET-1 on AVN cellular electrophysiology. METHODS: Electrophysiological experiments were conducted in which recordings were made from rabbit isolated AVN cells at 35–37°C using the whole-cell patch clamp recording technique. RESULTS: Application of ET-1 (10 nM) to spontaneously active AVN cells led rapidly (within ∼13 s) to membrane potential hyperpolarisation and cessation of spontaneous action potentials (APs). This effect was prevented by pre-application of the ET(A) receptor inhibitor BQ-123 (1 µM) and was not mimicked by the ET(B) receptor agonist IRL-1620 (300 nM). In whole-cell voltage-clamp experiments, ET-1 partially inhibited L-type calcium current (I(Ca,L)) and rapid delayed rectifier K(+) current (I(Kr)), whilst it transiently activated the hyperpolarisation-activated current (I(f)) at voltages negative to the pacemaking range, and activated an inwardly rectifying current that was inhibited by both tertiapin-Q (300 nM) and Ba(2+) ions (2 mM); each of these effects was sensitive to ET(A) receptor inhibition. In cells exposed to tertiapin-Q, ET-1 application did not produce membrane potential hyperpolarisation or immediate cessation of spontaneous activity; instead, there was a progressive decline in AP amplitude and depolarisation of maximum diastolic potential. CONCLUSIONS: Acutely applied ET-1 exerts a direct modulatory effect on AVN cell electrophysiology. The dominant effect of ET-1 in this study was activation of a tertiapin-Q sensitive inwardly rectifying K(+) current via ET(A) receptors, which led rapidly to cell quiescence. |
format | Online Article Text |
id | pubmed-3315568 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33155682012-04-04 Modulation by Endothelin-1 of Spontaneous Activity and Membrane Currents of Atrioventricular Node Myocytes from the Rabbit Heart Choisy, Stéphanie C. Cheng, Hongwei Smith, Godfrey L. James, Andrew F. Hancox, Jules C. PLoS One Research Article BACKGROUND: The atrioventricular node (AVN) is a key component of the cardiac pacemaker-conduction system. Although it is known that receptors for the peptide hormone endothelin-1 (ET-1) are expressed in the AVN, there is very little information available on the modulatory effects of ET-1 on AVN electrophysiology. This study characterises for the first time acute modulatory effects of ET-1 on AVN cellular electrophysiology. METHODS: Electrophysiological experiments were conducted in which recordings were made from rabbit isolated AVN cells at 35–37°C using the whole-cell patch clamp recording technique. RESULTS: Application of ET-1 (10 nM) to spontaneously active AVN cells led rapidly (within ∼13 s) to membrane potential hyperpolarisation and cessation of spontaneous action potentials (APs). This effect was prevented by pre-application of the ET(A) receptor inhibitor BQ-123 (1 µM) and was not mimicked by the ET(B) receptor agonist IRL-1620 (300 nM). In whole-cell voltage-clamp experiments, ET-1 partially inhibited L-type calcium current (I(Ca,L)) and rapid delayed rectifier K(+) current (I(Kr)), whilst it transiently activated the hyperpolarisation-activated current (I(f)) at voltages negative to the pacemaking range, and activated an inwardly rectifying current that was inhibited by both tertiapin-Q (300 nM) and Ba(2+) ions (2 mM); each of these effects was sensitive to ET(A) receptor inhibition. In cells exposed to tertiapin-Q, ET-1 application did not produce membrane potential hyperpolarisation or immediate cessation of spontaneous activity; instead, there was a progressive decline in AP amplitude and depolarisation of maximum diastolic potential. CONCLUSIONS: Acutely applied ET-1 exerts a direct modulatory effect on AVN cell electrophysiology. The dominant effect of ET-1 in this study was activation of a tertiapin-Q sensitive inwardly rectifying K(+) current via ET(A) receptors, which led rapidly to cell quiescence. Public Library of Science 2012-03-29 /pmc/articles/PMC3315568/ /pubmed/22479400 http://dx.doi.org/10.1371/journal.pone.0033448 Text en Choisy et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Choisy, Stéphanie C. Cheng, Hongwei Smith, Godfrey L. James, Andrew F. Hancox, Jules C. Modulation by Endothelin-1 of Spontaneous Activity and Membrane Currents of Atrioventricular Node Myocytes from the Rabbit Heart |
title | Modulation by Endothelin-1 of Spontaneous Activity and Membrane Currents of Atrioventricular Node Myocytes from the Rabbit Heart |
title_full | Modulation by Endothelin-1 of Spontaneous Activity and Membrane Currents of Atrioventricular Node Myocytes from the Rabbit Heart |
title_fullStr | Modulation by Endothelin-1 of Spontaneous Activity and Membrane Currents of Atrioventricular Node Myocytes from the Rabbit Heart |
title_full_unstemmed | Modulation by Endothelin-1 of Spontaneous Activity and Membrane Currents of Atrioventricular Node Myocytes from the Rabbit Heart |
title_short | Modulation by Endothelin-1 of Spontaneous Activity and Membrane Currents of Atrioventricular Node Myocytes from the Rabbit Heart |
title_sort | modulation by endothelin-1 of spontaneous activity and membrane currents of atrioventricular node myocytes from the rabbit heart |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315568/ https://www.ncbi.nlm.nih.gov/pubmed/22479400 http://dx.doi.org/10.1371/journal.pone.0033448 |
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