Upregulation of SK3 and IK1 channels contributes to the enhanced endothelial calcium signaling and the preserved coronary relaxation in obese Zucker rats.

<h4>Background and aims</h4>Endothelial small- and intermediate-conductance KCa channels, SK3 and IK1, are key mediators in the endothelium-derived hyperpolarization and relaxation of vascular smooth muscle and also in the modulation of endothelial Ca2+ signaling and nitric oxide (NO) re...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Belén Climent, Laura Moreno, Pilar Martínez, Cristina Contreras, Ana Sánchez, Francisco Pérez-Vizcaíno, Albino García-Sacristán, Luis Rivera, Dolores Prieto
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d39e580b192145d9bede6cb891057c6a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d39e580b192145d9bede6cb891057c6a
record_format	dspace
spelling	oai:doaj.org-article:d39e580b192145d9bede6cb891057c6a2021-11-25T05:57:10ZUpregulation of SK3 and IK1 channels contributes to the enhanced endothelial calcium signaling and the preserved coronary relaxation in obese Zucker rats.1932-620310.1371/journal.pone.0109432https://doaj.org/article/d39e580b192145d9bede6cb891057c6a2014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0109432https://doaj.org/toc/1932-6203<h4>Background and aims</h4>Endothelial small- and intermediate-conductance KCa channels, SK3 and IK1, are key mediators in the endothelium-derived hyperpolarization and relaxation of vascular smooth muscle and also in the modulation of endothelial Ca2+ signaling and nitric oxide (NO) release. Obesity is associated with endothelial dysfunction and impaired relaxation, although how obesity influences endothelial SK3/IK1 function is unclear. Therefore we assessed whether the role of these channels in the coronary circulation is altered in obese animals.<h4>Methods and results</h4>In coronary arteries mounted in microvascular myographs, selective blockade of SK3/IK1 channels unmasked an increased contribution of these channels to the ACh- and to the exogenous NO- induced relaxations in arteries of Obese Zucker Rats (OZR) compared to Lean Zucker Rats (LZR). Relaxant responses induced by the SK3/IK1 channel activator NS309 were enhanced in OZR and NO- endothelium-dependent in LZR, whereas an additional endothelium-independent relaxant component was found in OZR. Fura2-AM fluorescence revealed a larger ACh-induced intracellular Ca2+ mobilization in the endothelium of coronary arteries from OZR, which was inhibited by blockade of SK3/IK1 channels in both LZR and OZR. Western blot analysis showed an increased expression of SK3/IK1 channels in coronary arteries of OZR and immunohistochemistry suggested that it takes place predominantly in the endothelial layer.<h4>Conclusions</h4>Obesity may induce activation of adaptive vascular mechanisms to preserve the dilator function in coronary arteries. Increased function and expression of SK3/IK1 channels by influencing endothelial Ca2+ dynamics might contribute to the unaltered endothelium-dependent coronary relaxation in the early stages of obesity.Belén ClimentLaura MorenoPilar MartínezCristina ContrerasAna SánchezFrancisco Pérez-VizcaínoAlbino García-SacristánLuis RiveraDolores PrietoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 10, p e109432 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Belén Climent Laura Moreno Pilar Martínez Cristina Contreras Ana Sánchez Francisco Pérez-Vizcaíno Albino García-Sacristán Luis Rivera Dolores Prieto Upregulation of SK3 and IK1 channels contributes to the enhanced endothelial calcium signaling and the preserved coronary relaxation in obese Zucker rats.
description	<h4>Background and aims</h4>Endothelial small- and intermediate-conductance KCa channels, SK3 and IK1, are key mediators in the endothelium-derived hyperpolarization and relaxation of vascular smooth muscle and also in the modulation of endothelial Ca2+ signaling and nitric oxide (NO) release. Obesity is associated with endothelial dysfunction and impaired relaxation, although how obesity influences endothelial SK3/IK1 function is unclear. Therefore we assessed whether the role of these channels in the coronary circulation is altered in obese animals.<h4>Methods and results</h4>In coronary arteries mounted in microvascular myographs, selective blockade of SK3/IK1 channels unmasked an increased contribution of these channels to the ACh- and to the exogenous NO- induced relaxations in arteries of Obese Zucker Rats (OZR) compared to Lean Zucker Rats (LZR). Relaxant responses induced by the SK3/IK1 channel activator NS309 were enhanced in OZR and NO- endothelium-dependent in LZR, whereas an additional endothelium-independent relaxant component was found in OZR. Fura2-AM fluorescence revealed a larger ACh-induced intracellular Ca2+ mobilization in the endothelium of coronary arteries from OZR, which was inhibited by blockade of SK3/IK1 channels in both LZR and OZR. Western blot analysis showed an increased expression of SK3/IK1 channels in coronary arteries of OZR and immunohistochemistry suggested that it takes place predominantly in the endothelial layer.<h4>Conclusions</h4>Obesity may induce activation of adaptive vascular mechanisms to preserve the dilator function in coronary arteries. Increased function and expression of SK3/IK1 channels by influencing endothelial Ca2+ dynamics might contribute to the unaltered endothelium-dependent coronary relaxation in the early stages of obesity.
format	article
author	Belén Climent Laura Moreno Pilar Martínez Cristina Contreras Ana Sánchez Francisco Pérez-Vizcaíno Albino García-Sacristán Luis Rivera Dolores Prieto
author_facet	Belén Climent Laura Moreno Pilar Martínez Cristina Contreras Ana Sánchez Francisco Pérez-Vizcaíno Albino García-Sacristán Luis Rivera Dolores Prieto
author_sort	Belén Climent
title	Upregulation of SK3 and IK1 channels contributes to the enhanced endothelial calcium signaling and the preserved coronary relaxation in obese Zucker rats.
title_short	Upregulation of SK3 and IK1 channels contributes to the enhanced endothelial calcium signaling and the preserved coronary relaxation in obese Zucker rats.
title_full	Upregulation of SK3 and IK1 channels contributes to the enhanced endothelial calcium signaling and the preserved coronary relaxation in obese Zucker rats.
title_fullStr	Upregulation of SK3 and IK1 channels contributes to the enhanced endothelial calcium signaling and the preserved coronary relaxation in obese Zucker rats.
title_full_unstemmed	Upregulation of SK3 and IK1 channels contributes to the enhanced endothelial calcium signaling and the preserved coronary relaxation in obese Zucker rats.
title_sort	upregulation of sk3 and ik1 channels contributes to the enhanced endothelial calcium signaling and the preserved coronary relaxation in obese zucker rats.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/d39e580b192145d9bede6cb891057c6a
work_keys_str_mv	AT belencliment upregulationofsk3andik1channelscontributestotheenhancedendothelialcalciumsignalingandthepreservedcoronaryrelaxationinobesezuckerrats AT lauramoreno upregulationofsk3andik1channelscontributestotheenhancedendothelialcalciumsignalingandthepreservedcoronaryrelaxationinobesezuckerrats AT pilarmartinez upregulationofsk3andik1channelscontributestotheenhancedendothelialcalciumsignalingandthepreservedcoronaryrelaxationinobesezuckerrats AT cristinacontreras upregulationofsk3andik1channelscontributestotheenhancedendothelialcalciumsignalingandthepreservedcoronaryrelaxationinobesezuckerrats AT anasanchez upregulationofsk3andik1channelscontributestotheenhancedendothelialcalciumsignalingandthepreservedcoronaryrelaxationinobesezuckerrats AT franciscoperezvizcaino upregulationofsk3andik1channelscontributestotheenhancedendothelialcalciumsignalingandthepreservedcoronaryrelaxationinobesezuckerrats AT albinogarciasacristan upregulationofsk3andik1channelscontributestotheenhancedendothelialcalciumsignalingandthepreservedcoronaryrelaxationinobesezuckerrats AT luisrivera upregulationofsk3andik1channelscontributestotheenhancedendothelialcalciumsignalingandthepreservedcoronaryrelaxationinobesezuckerrats AT doloresprieto upregulationofsk3andik1channelscontributestotheenhancedendothelialcalciumsignalingandthepreservedcoronaryrelaxationinobesezuckerrats
_version_	1718414369739505664

Upregulation of SK3 and IK1 channels contributes to the enhanced endothelial calcium signaling and the preserved coronary relaxation in obese Zucker rats.

Ejemplares similares