ArticleBritish journal of pharmacology2012
Pharmacological activation of KCa3.1/KCa2.3 channels produces endothelial hyperpolarization and lowers blood pressure in conscious dogs.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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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
48 citing papers in PubMed, 66 citations in OpenAlex.
- Structural basis for the subtype-selective activation of KStructure (London, England : 1993) · 2026Article
- Potassium channel-targeted therapy in reducing vascular complications in diabetes mellitus: novel insights.Frontiers in pharmacology · 2026Review
- VX-445 (elexacaftor) inhibits chloride secretion across human bronchial epithelial cells by directly blocking KCa3.1 channels.PNAS nexus · 2025Article
- Potentiation of BKCa channels by cystic fibrosis transmembrane conductance regulator correctors VX-445 and VX-121.The Journal of clinical investigation · 2024Article
- CaInternational journal of molecular sciences · 2023Review
- Endothelial IK and SK channel activation decreases pulmonary arterial pressure and vascular remodeling in pulmonary hypertension.Pulmonary circulation · 2023Article
- Histone deacetylase inhibitors (HDACi) increase expression of KCa2.3 (SK3) in primary microvascular endothelial cells.American journal of physiology. Cell physiology · 2022Article
- Role of SNARE Proteins in the Insertion of KCa3.1 in the Plasma Membrane of a Polarized Epithelium.Frontiers in physiology · 2022Article
- Effect of the KCa3.1 blocker, senicapoc, on cerebral edema and cardiovascular function after cardiac arrest - A randomized experimental rat study.Resuscitation plus · 2021Article
- KCa channel activation normalizes endothelial function in Type 2 Diabetic resistance arteries by improving intracellular CaMetabolism: clinical and experimental · 2021Article
- Crocin Improves Endothelial Mitochondrial DysfunctionFrontiers in cell and developmental biology · 2021Article
- Small and intermediate CaHeart and vessels · 2020Article
- Pharmacology of Small- and Intermediate-Conductance Calcium-Activated Potassium Channels.Annual review of pharmacology and toxicology · 2020Review
- SKA-31, an activator of CaPharmacological research · 2020Article
- Modulation of Cardiovascular Function in Primary Hypertension in Rat by SKA-31, an Activator ofInternational journal of molecular sciences · 2019Article
- Pharmacological Targeting of KCa Channels to Improve Endothelial Function in the Spontaneously Hypertensive Rat.International journal of molecular sciences · 2019Article
- Pharmacologic targeting of endothelial CaChannels (Austin, Tex.) · 2018Review
- Structural insights into the potency of SK channel positive modulators.Scientific reports · 2017Article
- Down-regulation of KScientific reports · 2017Article
- Calcium and electrical signaling in arterial endothelial tubes: New insights into cellular physiology and cardiovascular function.Microcirculation (New York, N.Y. : 1994) · 2017Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
background and purposeIn rodents, the endothelial KCa channels, KCa3.1 and KCa2.3, have been shown to play a crucial role in initiating endothelium-derived hyperpolarizing factor (EDHF) vasodilator responses. However, it is not known to what extent these channels are involved in blood pressure regulation in large mammals, which would also allow us to address safety issues. We therefore characterized canine endothelial KCa3.1 and KCa2.3 functions and evaluated the effect of the KCa3.1/KCa2.3 activator SKA-31 on blood pressure and heart rate in dogs. EXPERIMENTAL APPROACH: Canine endothelial KCa3.1/KCa2.3 functions were studied by patch-clamp electrophysiology and wire myography in mesenteric arteries. Systemic cardiovascular actions of acute SKA-31 administration were monitored in conscious, unstressed beagle dogs. KEY
resultsMesenteric endothelial cells expressed functional KCa3.1 and KCa2.3 channels that were strongly activated by SKA-31. SKA-31 hyperpolarized the endothelial membrane and doubled endothelial hyperpolarization-dependent vasodilator responses in mesenteric arteries. SKA-31 (2 mg·kg(-1), i.v.) rapidly decreased the MAP by 28 ± 6 mmHg; this response was transient (8 ± 1 s), and the initial drop was followed by a fast and pronounced increase in HR (+109 ± 7 beats min(-1)) reflecting baroreceptor activation. SKA-31 significantly augmented similar transient depressor responses elicited by ACh (20 ng·kg(-1)) and doubled the magnitude of the response over time. CONCLUSIONS AND IMPLICATIONS: Activation of endothelial KCa3.1 and KCa2.3 lowers arterial blood pressure in dogs by an immediate electrical vasodilator mechanism. The results support the concept that pharmacological activation of these channels may represent a potential unique endothelium-specific antihypertensive therapy.
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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.