ArticleAmerican journal of physiology. Heart and circulatory physiology2016
Endothelial SK3 channel-associated Ca2+ microdomains modulate blood pressure.
Article in American journal of physiology. Heart and circulatory physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Redox Regulation of KAntioxidants & redox signaling · 2024Review
- Intravenous anesthetics have differential effects on human potassium channels.Acta biochimica et biophysica Sinica · 2024Article
- Vasodilators mobilize SK3 channels in endothelial cells to produce arterial relaxation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- CaInternational journal of molecular sciences · 2023Review
- Histone deacetylase inhibitors (HDACi) increase expression of KCa2.3 (SK3) in primary microvascular endothelial cells.American journal of physiology. Cell physiology · 2022Article
- Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3-a subgroup of KEuropean journal of human genetics : EJHG · 2021Article
- A single-nucleotide change underlies the genetic assimilation of a plastic trait.Science advances · 2021Article
- Polarized Proteins in Endothelium and Their Contribution to Function.Journal of vascular research · 2021Review
- Critical regulation of atherosclerosis by the KCa3.1 channel and the retargeting of this therapeutic target in in-stent neoatherosclerosis.Journal of molecular medicine (Berlin, Germany) · 2019Review
- Gain-of-Function Mutations in KCNN3 Encoding the Small-Conductance CaAmerican journal of human genetics · 2019Article
- Functional Interaction among KInternational journal of molecular sciences · 2019Review
- Caveolae facilitate TRPV4-mediated CaAmerican journal of physiology. Renal physiology · 2018Article
- Sex-Specific Mechanisms of Resistance Vessel Endothelial Dysfunction Induced by Cardiometabolic Risk Factors.Journal of the American Heart Association · 2018Article
- TRPV4 regulates migration and tube formation of human retinal capillary endothelial cells.BMC ophthalmology · 2018Article
- Down-regulation of KScientific reports · 2017Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Activation of vascular endothelial small- (KCa2.3, SK3) or intermediate- (KCa3.1, IK1) conductance Ca(2+)-activated potassium channels induces vasorelaxation via an endothelium-derived hyperpolarization (EDH) pathway. Although the activation of SK3 and IK1 channels converges on EDH, their subcellular effects on signal transduction are different and not completely clear. In this study, a novel endothelium-specific SK3 knockout (SK3(-/-)) mouse model was utilized to specifically examine the contribution of SK3 channels to mesenteric artery vasorelaxation, endothelial Ca(2+) dynamics, and blood pressure. The absence of SK3 expression was confirmed using real-time quantitative PCR and Western blot analysis. Functional studies showed impaired EDH-mediated vasorelaxation in SK3(-/-) small mesenteric arteries. Immunostaining results from SK3(-/-) vessels confirmed the absence of SK3 and further showed altered distribution of transient receptor potential channels, type 4 (TRPV4). Electrophysiological recordings showed a lack of SK3 channel activity, while TRPV4-IK1 channel coupling remained intact in SK3(-/-) endothelial cells. Moreover, Ca(2+) imaging studies in SK3(-/-) endothelium showed increased Ca(2+) transients with reduced amplitude and duration under basal conditions. Importantly, SK3(-/-) endothelium lacked a distinct type of Ca(2+) dynamic that is sensitive to TRPV4 activation. Blood pressure measurements showed that the SK3(-/-) mice were hypertensive, and the blood pressure increase was further enhanced during the 12-h dark cycle when animals are most active. Taken together, our results reveal a previously unappreciated SK3 signaling microdomain that modulates endothelial Ca(2+) dynamics, vascular tone, and blood pressure.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.