ArticleJournal of the American Heart Association2013
Hypotension due to Kir6.1 gain-of-function in vascular smooth muscle.
Article in Journal of the American Heart Association, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 71 citations in OpenAlex.
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- Functional expression of inwardly rectifying and ATP-sensitive potassium channels in human pulmonary artery smooth muscle and endothelial cells.The Journal of physiology · 2026Article
- Characterization of four structurally diverse inhibitors of SUR2-containing KChannels (Austin, Tex.) · 2024Article
- Electrophysiology of Human iPSC-derived Vascular Smooth Muscle Cells and Cell-autonomous Consequences of Cantú Syndrome Mutations.Function (Oxford, England) · 2024Article
- Mitochondrial Ca2+-coupled generation of reactive oxygen species, peroxynitrite formation, and endothelial dysfunction in Cantú syndrome.JCI insight · 2024Article
- Effect of Type-2 Diabetes Mellitus on the Expression and Function of Smooth Muscle ATP-Sensitive Potassium Channels in Human Internal Mammary Artery Grafts.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Novel loss-of-function variants expand ABCC9-related intellectual disability and myopathy syndrome.Brain : a journal of neurology · 2024Article
- Discovery and Characterization of VU0542270, the First Selective Inhibitor of Vascular Kir6.1/SUR2B KMolecular pharmacology · 2024Article
- Rapid Characterization of the Functional and Pharmacological Consequences of Cantú Syndrome KThe Journal of pharmacology and experimental therapeutics · 2023Article
- Skeletal muscle delimited myopathy and verapamil toxicity in SUR2 mutant mouse models of AIMS.EMBO molecular medicine · 2023Article
- Overactive ATP-Sensitive KFunction (Oxford, England) · 2023Article
- KAmerican journal of physiology. Cell physiology · 2022Review
- Kir6.1 and SUR2B in Cantú syndrome.American journal of physiology. Cell physiology · 2022Review
- Potassium Channels in the Uterine Vasculature: Role in Healthy and Complicated Pregnancies.International journal of molecular sciences · 2022Review
- Adenosine signaling activates ATP-sensitive KScience signaling · 2022Article
- ATP-sensitive potassium channels in zebrafish cardiac and vascular smooth muscle.The Journal of physiology · 2022Article
- Functional Regulation of KFrontiers in pharmacology · 2022Review
- Complex consequences of Cantu syndrome SUR2 variant R1154Q in genetically modified mice.JCI insight · 2021Article
- Novel cholesterol-dependent regulation of cardiac KPhysiological reports · 2021Article
- Review
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
backgroundKATP channels, assembled from pore-forming (Kir6.1 or Kir6.2) and regulatory (SUR1 or SUR2) subunits, link metabolism to excitability. Loss of Kir6.2 results in hypoglycemia and hyperinsulinemia, whereas loss of Kir6.1 causes Prinzmetal angina-like symptoms in mice. Conversely, overactivity of Kir6.2 induces neonatal diabetes in mice and humans, but consequences of Kir6.1 overactivity are unknown. METHODS AND
resultsWe generated transgenic mice expressing wild-type (WT), ATP-insensitive Kir6.1 [Gly343Asp] (GD), and ATP-insensitive Kir6.1 [Gly343Asp,Gln53Arg] (GD-QR) subunits, under Cre-recombinase control. Expression was induced in smooth muscle cells by crossing with smooth muscle myosin heavy chain promoter-driven tamoxifen-inducible Cre-recombinase (SMMHC-Cre-ER) mice. Three weeks after tamoxifen induction, we assessed blood pressure in anesthetized and conscious animals, as well as contractility of mesenteric artery smooth muscle and KATP currents in isolated mesenteric artery myocytes. Both systolic and diastolic blood pressures were significantly reduced in GD and GD-QR mice but normal in mice expressing the WT transgene and elevated in Kir6.1 knockout mice as well as in mice expressing dominant-negative Kir6.1 [AAA] in smooth muscle. Contractile response of isolated GD-QR mesenteric arteries was blunted relative to WT controls, but nitroprusside relaxation was unaffected. Basal KATP conductance and pinacidil-activated conductance were elevated in GD but not in WT myocytes.
conclusionsKATP overactivity in vascular muscle can lead directly to reduced vascular contractility and lower blood pressure. We predict that gain of vascular KATP function in humans would lead to a chronic vasodilatory phenotype, as indeed has recently been demonstrated in Cantu syndrome.
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