ArticleThe Journal of general physiology2015
Differential mechanisms of Cantú syndrome-associated gain of function mutations in the ABCC9 (SUR2) subunit of the KATP channel.
Article in The Journal of general physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- Myocardial protection by adenosine triphosphate-sensitive potassium channel opener diazoxide involves sulfonylurea receptor 2 subunit.JTCVS open · 2026Article
- Muscle fatigue arising intrinsically from SUR2- but not Kir6.1-dependent gain-of-function in Cantu syndrome mice.The Journal of general physiology · 2025Article
- Gain-of-function mutations in KATP channel subunits compromise colonic tight junction integrity and epithelial homeostasis in murine models of Cantú syndrome.Frontiers in medicine · 2025Article
- A novel ABCC9 variant in a Greek family with Cantu syndrome affecting multiple generations highlights the functional role of the SUR2B NBD1.American journal of medical genetics. Part A · 2024Article
- Mitochondrial Ca2+-coupled generation of reactive oxygen species, peroxynitrite formation, and endothelial dysfunction in Cantú syndrome.JCI insight · 2024Article
- Rapid Characterization of the Functional and Pharmacological Consequences of Cantú Syndrome KThe Journal of pharmacology and experimental therapeutics · 2023Article
- Article
- Personalized Therapeutics for KAnnual review of pharmacology and toxicology · 2023Review
- A Cantú syndrome mutation produces dual effects on KATP channels by disrupting ankyrin B regulation.The Journal of general physiology · 2023Article
- Kir6.1 and SUR2B in Cantú syndrome.American journal of physiology. Cell physiology · 2022Review
- Localized islet nuclear enlargement hyperinsulinism (LINE-HI) due to ABCC8 and GCK mosaic mutations.European journal of endocrinology · 2022Article
- ATP-sensitive potassium channels in zebrafish cardiac and vascular smooth muscle.The Journal of physiology · 2022Article
- Consequences of SUR2[A478V] Mutation in Skeletal Muscle of Murine Model of Cantu Syndrome.Cells · 2021Article
- Complex consequences of Cantu syndrome SUR2 variant R1154Q in genetically modified mice.JCI insight · 2021Article
- The Pharmacology of ATP-Sensitive KHandbook of experimental pharmacology · 2021Article
- Glibenclamide reverses cardiovascular abnormalities of Cantu syndrome driven by KATP channel overactivity.The Journal of clinical investigation · 2020Article
- Pathophysiological Consequences of KATP Channel Overactivity and Pharmacological Response to Glibenclamide in Skeletal Muscle of a Murine Model of Cantù Syndrome.Frontiers in pharmacology · 2020Article
- Novel dominant KAmerican journal of medical genetics. Part A · 2019Article
- ABCC9-related Intellectual disability Myopathy Syndrome is a KNature communications · 2019Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cantú syndrome (CS) is a rare disease characterized by congenital hypertrichosis, distinct facial features, osteochondrodysplasia, and cardiac defects. Recent genetic analysis has revealed that the majority of CS patients carry a missense mutation in ABCC9, which codes for the sulfonylurea receptor SUR2. SUR2 subunits couple with Kir6.x, inwardly rectifying potassium pore-forming subunits, to form adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels, which link cell metabolism to membrane excitability in a variety of tissues including vascular smooth muscle, skeletal muscle, and the heart. The functional consequences of multiple uncharacterized CS mutations remain unclear. Here, we have focused on determining the functional consequences of three documented human CS-associated ABCC9 mutations: human P432L, A478V, and C1043Y. The mutations were engineered in the equivalent position in rat SUR2A (P429L, A475V, and C1039Y), and each was coexpressed with mouse Kir6.2. Using macroscopic rubidium ((86)Rb(+)) efflux assays, we show that K(ATP) channels formed with P429L, A475V, or C1039Y mutants enhance K(ATP) activity compared with wild-type (WT) channels. We used inside-out patch-clamp electrophysiology to measure channel sensitivity to ATP inhibition and to MgADP activation. For P429L and A475V mutants, sensitivity to ATP inhibition was comparable to WT channels, but activation by MgADP was significantly greater. C1039Y-dependent channels were significantly less sensitive to inhibition by ATP or by glibenclamide, but MgADP activation was comparable to WT. The results indicate that these three CS mutations all lead to overactive K(ATP) channels, but at least two mechanisms underlie the observed gain of function: decreased ATP inhibition and enhanced MgADP activation.
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