Dual role of calcium-activated potassium channels of high conductance: facilitator or limiter of NO-induced arterial relaxation?

AimCalcium-activated potassium channels of high conductance (BKCa channels) are important contributors to vascular smooth muscle membrane potential and thus to vascular tone. BKCa channels can promote vasodilation by facilitating vessel responses to NO. BKCa channels may also serve as limiters of th...

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Main Authors: Anastasia A. Shvetsova, Dina K. Gaynullina, Johannes Schmid, Peter Winkler, Isabella Sonsala, Rudolf Schubert
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Physiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2025.1563014/full
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author Anastasia A. Shvetsova
Dina K. Gaynullina
Dina K. Gaynullina
Johannes Schmid
Johannes Schmid
Peter Winkler
Peter Winkler
Isabella Sonsala
Isabella Sonsala
Rudolf Schubert
Rudolf Schubert
author_facet Anastasia A. Shvetsova
Dina K. Gaynullina
Dina K. Gaynullina
Johannes Schmid
Johannes Schmid
Peter Winkler
Peter Winkler
Isabella Sonsala
Isabella Sonsala
Rudolf Schubert
Rudolf Schubert
author_sort Anastasia A. Shvetsova
collection DOAJ
description AimCalcium-activated potassium channels of high conductance (BKCa channels) are important contributors to vascular smooth muscle membrane potential and thus to vascular tone. BKCa channels can promote vasodilation by facilitating vessel responses to NO. BKCa channels may also serve as limiters of the anticontractile effect of NO. However, it is unclear whether BKCa channels act simultaneously as facilitators and limiters in different vascular regions. Therefore, this study tested the hypothesis that BKCa channels both facilitate and limit NO-induced vasorelaxation in multiple vessels.MethodsContractile responses of rat tail, saphenous, and left and right coronary arteries were studied using wire myography.ResultsThe NO-donor SNP reduced contractile responses induced by low concentrations of methoxamine or serotonin, respectively, in all arteries tested, both in the absence and in the presence of iberiotoxin. This anticontractile effect of SNP was larger in the presence of iberiotoxin than in its absence, i.e., functionally active BKCa channels limit the anticontractile effect of SNP. In contrast, the anticontractile effect of SNP at high concentrations of methoxamine or serotonin, respectively, in all arteries tested was smaller in the presence of iberiotoxin than in its absence, i.e., functionally active BKCa channels facilitate the anticontractile effect of SNP.ConclusionBKCa channels simultaneously limit NO-induced vasodilation at lower levels of contractility but facilitate it at higher levels of contractility in multiple vascular beds. Therefore, BKCa channels may play a dual role as facilitators and as limiters of the effect of NO, depending on the level of contractility.
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spelling doaj-art-e4f3e9cb6d4b45c18eb09bb3e58f84302025-08-20T02:49:36ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2025-03-011610.3389/fphys.2025.15630141563014Dual role of calcium-activated potassium channels of high conductance: facilitator or limiter of NO-induced arterial relaxation?Anastasia A. Shvetsova0Dina K. Gaynullina1Dina K. Gaynullina2Johannes Schmid3Johannes Schmid4Peter Winkler5Peter Winkler6Isabella Sonsala7Isabella Sonsala8Rudolf Schubert9Rudolf Schubert10Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, RussiaFaculty of Biology, M.V. Lomonosov Moscow State University, Moscow, RussiaInsitute of Physiology, Russian National Research Medical University, Moscow, RussiaPhysiology, Faculty of Medicine, Institute of Theoretical Medicine, University of Augsburg, Augsburg, GermanyResearch Division Cardiovascular Physiology, Medical Faculty Mannheim, European Center of Angioscience (ECAS), Heidelberg University, Mannheim, GermanyPhysiology, Faculty of Medicine, Institute of Theoretical Medicine, University of Augsburg, Augsburg, GermanyResearch Division Cardiovascular Physiology, Medical Faculty Mannheim, European Center of Angioscience (ECAS), Heidelberg University, Mannheim, GermanyPhysiology, Faculty of Medicine, Institute of Theoretical Medicine, University of Augsburg, Augsburg, GermanyResearch Division Cardiovascular Physiology, Medical Faculty Mannheim, European Center of Angioscience (ECAS), Heidelberg University, Mannheim, GermanyPhysiology, Faculty of Medicine, Institute of Theoretical Medicine, University of Augsburg, Augsburg, GermanyResearch Division Cardiovascular Physiology, Medical Faculty Mannheim, European Center of Angioscience (ECAS), Heidelberg University, Mannheim, GermanyAimCalcium-activated potassium channels of high conductance (BKCa channels) are important contributors to vascular smooth muscle membrane potential and thus to vascular tone. BKCa channels can promote vasodilation by facilitating vessel responses to NO. BKCa channels may also serve as limiters of the anticontractile effect of NO. However, it is unclear whether BKCa channels act simultaneously as facilitators and limiters in different vascular regions. Therefore, this study tested the hypothesis that BKCa channels both facilitate and limit NO-induced vasorelaxation in multiple vessels.MethodsContractile responses of rat tail, saphenous, and left and right coronary arteries were studied using wire myography.ResultsThe NO-donor SNP reduced contractile responses induced by low concentrations of methoxamine or serotonin, respectively, in all arteries tested, both in the absence and in the presence of iberiotoxin. This anticontractile effect of SNP was larger in the presence of iberiotoxin than in its absence, i.e., functionally active BKCa channels limit the anticontractile effect of SNP. In contrast, the anticontractile effect of SNP at high concentrations of methoxamine or serotonin, respectively, in all arteries tested was smaller in the presence of iberiotoxin than in its absence, i.e., functionally active BKCa channels facilitate the anticontractile effect of SNP.ConclusionBKCa channels simultaneously limit NO-induced vasodilation at lower levels of contractility but facilitate it at higher levels of contractility in multiple vascular beds. Therefore, BKCa channels may play a dual role as facilitators and as limiters of the effect of NO, depending on the level of contractility.https://www.frontiersin.org/articles/10.3389/fphys.2025.1563014/fullvasodilationarterial smooth muscleBK channelnitric oxidetail arterysaphenous artery
spellingShingle Anastasia A. Shvetsova
Dina K. Gaynullina
Dina K. Gaynullina
Johannes Schmid
Johannes Schmid
Peter Winkler
Peter Winkler
Isabella Sonsala
Isabella Sonsala
Rudolf Schubert
Rudolf Schubert
Dual role of calcium-activated potassium channels of high conductance: facilitator or limiter of NO-induced arterial relaxation?
Frontiers in Physiology
vasodilation
arterial smooth muscle
BK channel
nitric oxide
tail artery
saphenous artery
title Dual role of calcium-activated potassium channels of high conductance: facilitator or limiter of NO-induced arterial relaxation?
title_full Dual role of calcium-activated potassium channels of high conductance: facilitator or limiter of NO-induced arterial relaxation?
title_fullStr Dual role of calcium-activated potassium channels of high conductance: facilitator or limiter of NO-induced arterial relaxation?
title_full_unstemmed Dual role of calcium-activated potassium channels of high conductance: facilitator or limiter of NO-induced arterial relaxation?
title_short Dual role of calcium-activated potassium channels of high conductance: facilitator or limiter of NO-induced arterial relaxation?
title_sort dual role of calcium activated potassium channels of high conductance facilitator or limiter of no induced arterial relaxation
topic vasodilation
arterial smooth muscle
BK channel
nitric oxide
tail artery
saphenous artery
url https://www.frontiersin.org/articles/10.3389/fphys.2025.1563014/full
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