Impairment of Coronary Endothelial Function by Hypoxia-Reoxygenation Involves TRPC3 Inhibition-mediated KCa Channel Dysfunction: Implication in Ischemia-Reperfusion Injury

Abstract Despite increasing knowledge of the significance of calcium-activated potassium (KCa) and canonical transient receptor potential (TRPC) channels in endothelial physiology, no studies so far have investigated the link between these two distinct types of channels in the control of vascular to...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Xiang-Chong Wang, Wen-Tao Sun, Jie Fu, Jun-Hao Huang, Cheuk-Man Yu, Malcolm John Underwood, Guo-Wei He, Qin Yang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/016672dfe50b4794818bf141d5ecbd1e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:016672dfe50b4794818bf141d5ecbd1e
record_format	dspace
spelling	oai:doaj.org-article:016672dfe50b4794818bf141d5ecbd1e2021-12-02T12:30:13ZImpairment of Coronary Endothelial Function by Hypoxia-Reoxygenation Involves TRPC3 Inhibition-mediated KCa Channel Dysfunction: Implication in Ischemia-Reperfusion Injury10.1038/s41598-017-06247-32045-2322https://doaj.org/article/016672dfe50b4794818bf141d5ecbd1e2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06247-3https://doaj.org/toc/2045-2322Abstract Despite increasing knowledge of the significance of calcium-activated potassium (KCa) and canonical transient receptor potential (TRPC) channels in endothelial physiology, no studies so far have investigated the link between these two distinct types of channels in the control of vascular tone in pathological conditions. We previously demonstrated that hypoxia-reoxygenation (H-R) inhibits endothelial KCa and TRPC3 channels in porcine coronary arteries (PCAs). The present study further investigated whether modulation of TRPC3 is involved in H-R-induced KCa channel inhibition and associated vasodilatory dysfunction using approaches of wire myography, whole-cell voltage-clamp, and coimmunoprecipitation. Pharmacological inhibition or siRNA silencing of TRPC3 significantly suppressed bradykinin-induced intermediate- and small-conductance KCa (IKCa and SKCa) currents in endothelial cells of PCAs (PCAECs). TRPC3 protein exists in physical association with neither IKCa nor SKCa. In H-R-exposed PCAECs, the response of IKCa and SKCa to bradykinin-stimulation and to TRPC3-inhibition was markedly weakened. Activation of TRPC3 channels restored H-R-suppressed KCa currents in association with an improved endothelium-derived hyperpolarizing factor (EDHF)-type vasorelaxation. We conclude that inhibition of TRPC3 channels contributes to H-R-induced suppression of KCa channel activity, which serves as a mechanism underlying coronary endothelial dysfunction in ischemia-reperfusion (I-R) injury and renders TRPC3 a potential target for endothelial protection in I-R conditions.Xiang-Chong WangWen-Tao SunJie FuJun-Hao HuangCheuk-Man YuMalcolm John UnderwoodGuo-Wei HeQin YangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiang-Chong Wang Wen-Tao Sun Jie Fu Jun-Hao Huang Cheuk-Man Yu Malcolm John Underwood Guo-Wei He Qin Yang Impairment of Coronary Endothelial Function by Hypoxia-Reoxygenation Involves TRPC3 Inhibition-mediated KCa Channel Dysfunction: Implication in Ischemia-Reperfusion Injury
description	Abstract Despite increasing knowledge of the significance of calcium-activated potassium (KCa) and canonical transient receptor potential (TRPC) channels in endothelial physiology, no studies so far have investigated the link between these two distinct types of channels in the control of vascular tone in pathological conditions. We previously demonstrated that hypoxia-reoxygenation (H-R) inhibits endothelial KCa and TRPC3 channels in porcine coronary arteries (PCAs). The present study further investigated whether modulation of TRPC3 is involved in H-R-induced KCa channel inhibition and associated vasodilatory dysfunction using approaches of wire myography, whole-cell voltage-clamp, and coimmunoprecipitation. Pharmacological inhibition or siRNA silencing of TRPC3 significantly suppressed bradykinin-induced intermediate- and small-conductance KCa (IKCa and SKCa) currents in endothelial cells of PCAs (PCAECs). TRPC3 protein exists in physical association with neither IKCa nor SKCa. In H-R-exposed PCAECs, the response of IKCa and SKCa to bradykinin-stimulation and to TRPC3-inhibition was markedly weakened. Activation of TRPC3 channels restored H-R-suppressed KCa currents in association with an improved endothelium-derived hyperpolarizing factor (EDHF)-type vasorelaxation. We conclude that inhibition of TRPC3 channels contributes to H-R-induced suppression of KCa channel activity, which serves as a mechanism underlying coronary endothelial dysfunction in ischemia-reperfusion (I-R) injury and renders TRPC3 a potential target for endothelial protection in I-R conditions.
format	article
author	Xiang-Chong Wang Wen-Tao Sun Jie Fu Jun-Hao Huang Cheuk-Man Yu Malcolm John Underwood Guo-Wei He Qin Yang
author_facet	Xiang-Chong Wang Wen-Tao Sun Jie Fu Jun-Hao Huang Cheuk-Man Yu Malcolm John Underwood Guo-Wei He Qin Yang
author_sort	Xiang-Chong Wang
title	Impairment of Coronary Endothelial Function by Hypoxia-Reoxygenation Involves TRPC3 Inhibition-mediated KCa Channel Dysfunction: Implication in Ischemia-Reperfusion Injury
title_short	Impairment of Coronary Endothelial Function by Hypoxia-Reoxygenation Involves TRPC3 Inhibition-mediated KCa Channel Dysfunction: Implication in Ischemia-Reperfusion Injury
title_full	Impairment of Coronary Endothelial Function by Hypoxia-Reoxygenation Involves TRPC3 Inhibition-mediated KCa Channel Dysfunction: Implication in Ischemia-Reperfusion Injury
title_fullStr	Impairment of Coronary Endothelial Function by Hypoxia-Reoxygenation Involves TRPC3 Inhibition-mediated KCa Channel Dysfunction: Implication in Ischemia-Reperfusion Injury
title_full_unstemmed	Impairment of Coronary Endothelial Function by Hypoxia-Reoxygenation Involves TRPC3 Inhibition-mediated KCa Channel Dysfunction: Implication in Ischemia-Reperfusion Injury
title_sort	impairment of coronary endothelial function by hypoxia-reoxygenation involves trpc3 inhibition-mediated kca channel dysfunction: implication in ischemia-reperfusion injury
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/016672dfe50b4794818bf141d5ecbd1e
work_keys_str_mv	AT xiangchongwang impairmentofcoronaryendothelialfunctionbyhypoxiareoxygenationinvolvestrpc3inhibitionmediatedkcachanneldysfunctionimplicationinischemiareperfusioninjury AT wentaosun impairmentofcoronaryendothelialfunctionbyhypoxiareoxygenationinvolvestrpc3inhibitionmediatedkcachanneldysfunctionimplicationinischemiareperfusioninjury AT jiefu impairmentofcoronaryendothelialfunctionbyhypoxiareoxygenationinvolvestrpc3inhibitionmediatedkcachanneldysfunctionimplicationinischemiareperfusioninjury AT junhaohuang impairmentofcoronaryendothelialfunctionbyhypoxiareoxygenationinvolvestrpc3inhibitionmediatedkcachanneldysfunctionimplicationinischemiareperfusioninjury AT cheukmanyu impairmentofcoronaryendothelialfunctionbyhypoxiareoxygenationinvolvestrpc3inhibitionmediatedkcachanneldysfunctionimplicationinischemiareperfusioninjury AT malcolmjohnunderwood impairmentofcoronaryendothelialfunctionbyhypoxiareoxygenationinvolvestrpc3inhibitionmediatedkcachanneldysfunctionimplicationinischemiareperfusioninjury AT guoweihe impairmentofcoronaryendothelialfunctionbyhypoxiareoxygenationinvolvestrpc3inhibitionmediatedkcachanneldysfunctionimplicationinischemiareperfusioninjury AT qinyang impairmentofcoronaryendothelialfunctionbyhypoxiareoxygenationinvolvestrpc3inhibitionmediatedkcachanneldysfunctionimplicationinischemiareperfusioninjury
_version_	1718394375829979136

Impairment of Coronary Endothelial Function by Hypoxia-Reoxygenation Involves TRPC3 Inhibition-mediated KCa Channel Dysfunction: Implication in Ischemia-Reperfusion Injury

Ejemplares similares