Functional Assembly of Kv7.1/Kv7.5 Channels With Emerging Properties on Vascular Muscle Physiology

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dc.contributor.authorOliveras, Anna
dc.contributor.authorRoura Ferrer, Meritxell
dc.contributor.authorSolé, Laura
dc.contributor.authorCruz, Alicia de la
dc.contributor.authorPrieto, Angela
dc.contributor.authorEtxebarria, Ainhoa
dc.contributor.authorManils, Joan
dc.contributor.authorMorales Cano, Daniel
dc.contributor.authorCondom, Enric
dc.contributor.authorSoler, Concepció
dc.contributor.authorCogolludo Torralba, Ángel Luis
dc.contributor.authorValenzuela, Carmen
dc.contributor.authorVillarroel, Alvaro
dc.contributor.authorComes, Núria
dc.contributor.authorFelipe, Antonio
dc.date.accessioned2024-01-31T09:19:36Z
dc.date.available2024-01-31T09:19:36Z
dc.date.issued2014-07
dc.description.abstractObjective—Voltage-dependent K+ (Kv) channels from the Kv7 family are expressed in blood vessels and contribute to cardiovascular physiology. Although Kv7 channel blockers trigger muscle contractions, Kv7 activators act as vasorelaxants. Kv7.1 and Kv7.5 are expressed in many vessels. Kv7.1 is under intense investigation because Kv7.1 blockers fail to modulate smooth muscle reactivity. In this study, we analyzed whether Kv7.1 and Kv7.5 may form functional heterotetrameric channels increasing the channel diversity in vascular smooth muscles. Approach and Results—Kv7.1 and Kv7.5 currents elicited in arterial myocytes, oocyte, and mammalian expression systems suggest the formation of heterotetrameric complexes. Kv7.1/Kv7.5 heteromers, exhibiting different pharmacological characteristics, participate in the arterial tone. Kv7.1/Kv7.5 associations were confirmed by coimmunoprecipitation, fluorescence resonance energy transfer, and fluorescence recovery after photobleaching experiments. Kv7.1/Kv7.5 heterotetramers were highly retained at the endoplasmic reticulum. Studies in HEK-293 cells, heart, brain, and smooth and skeletal muscles demonstrated that the predominant presence of Kv7.5 stimulates release of Kv7.1/Kv7.5 oligomers out of lipid raft microdomains. Electrophysiological studies supported that KCNE1 and KCNE3 regulatory subunits further increased the channel diversity. Finally, the analysis of rat isolated myocytes and human blood vessels demonstrated that Kv7.1 and Kv7.5 exhibited a differential expression, which may lead to channel diversity. Conclusions—Kv7.1 and Kv7.5 form heterotetrameric channels increasing the diversity of structures which fine-tune blood vessel reactivity. Because the lipid raft localization of ion channels is crucial for cardiovascular physiology, Kv7.1/Kv7.5 heteromers provide efficient spatial and temporal regulation of smooth muscle function. Our results shed light on the debate about the contribution of Kv7 channels to vasoconstriction and hypertension.
dc.description.departmentDepto. de Farmacología y Toxicología
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.statuspub
dc.identifier.citationOliveras A, Roura-Ferrer M, Solé L, de la Cruz A, Prieto A, Etxebarria A, Manils J, Morales-Cano D, Condom E, Soler C, Cogolludo A, Valenzuela C, Villarroel A, Comes N, Felipe A. Functional assembly of Kv7.1/Kv7.5 channels with emerging properties on vascular muscle physiology. Arterioscler Thromb Vasc Biol. 2014 Jul;34(7):1522-30. doi: 10.1161/ATVBAHA.114.303801
dc.identifier.doi10.1161/atvbaha.114.303801
dc.identifier.issn1079-5642
dc.identifier.issn1524-4636
dc.identifier.officialurlhttps://www.ahajournals.org/doi/10.1161/ATVBAHA.114.303801
dc.identifier.relatedurlhttps://pubmed.ncbi.nlm.nih.gov/24855057/
dc.identifier.urihttps://hdl.handle.net/20.500.14352/96920
dc.issue.number7
dc.journal.titleArteriosclerosis, Thrombosis, and Vascular Biology
dc.language.isoeng
dc.page.final1530
dc.page.initial1522
dc.publisherAmerican Heart Association
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.cdu612
dc.subject.keywordBlood vessels
dc.subject.keywordKCNQ1
dc.subject.keywordPotassium channel
dc.subject.keywordMuscle
dc.subject.keywordSmooth
dc.subject.ucmFisiología
dc.subject.unesco24 Ciencias de la Vida
dc.titleFunctional Assembly of Kv7.1/Kv7.5 Channels With Emerging Properties on Vascular Muscle Physiology
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number34
dspace.entity.typePublication
relation.isAuthorOfPublicationecbfa2d8-58e7-4222-83ea-b70445e2af6a
relation.isAuthorOfPublication.latestForDiscoveryecbfa2d8-58e7-4222-83ea-b70445e2af6a
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