ArticleBritish journal of pharmacology2009
Ca2+/calcineurin regulation of cloned vascular K ATP channels: crosstalk with the protein kinase A pathway.
Article in British journal of pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 38 citations in OpenAlex.
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- The Emerging Role of Endothelial Ion Channels in the Control of Human Microcirculation.International journal of molecular sciences · 2026Review
- A cellular atlas of calcineurin signaling.Biochimica et biophysica acta. Molecular cell research · 2023Review
- A Review of Calcineurin Biophysics with Implications for Cardiac Physiology.International journal of molecular sciences · 2021Review
- Role of ATP-sensitive potassium channels on hypoxic pulmonary vasoconstriction in endotoxemia.Respiratory research · 2018Article
- Potassium channels in the sinoatrial node and their role in heart rate control.Channels (Austin, Tex.) · 2018Review
- KATP Channels in the Cardiovascular System.Physiological reviews · 2016Review
- Article
- Calcineurin upregulates local Ca(2+) signaling through ryanodine receptor-1 in airway smooth muscle cells.American journal of physiology. Lung cellular and molecular physiology · 2014Article
- The role of ATP-sensitive potassium channels in cellular function and protection in the cardiovascular system.British journal of pharmacology · 2014Review
- No independent, but an interactive, role of calcium-activated potassium channels in human cutaneous active vasodilation.Journal of applied physiology (Bethesda, Md. : 1985) · 2013Article
- Splice cassette II of Na+,HCO3(-) cotransporter NBCn1 (slc4a7) interacts with calcineurin A: implications for transporter activity and intracellular pH control during rat artery contractions.The Journal of biological chemistry · 2013Article
- Rosiglitazone selectively inhibits K(ATP) channels by acting on the K(IR) 6 subunit.British journal of pharmacology · 2012Article
- K(ATP) channel action in vascular tone regulation: from genetics to diseases.Sheng li xue bao : [Acta physiologica Sinica] · 2012Review
- Cyclic nucleotide-dependent relaxation pathways in vascular smooth muscle.Cellular and molecular life sciences : CMLS · 2012Review
- Rosiglitazone inhibits vascular KATP channels and coronary vasodilation produced by isoprenaline.British journal of pharmacology · 2011Article
- Cardiomyocytes with disrupted CFTR function require CaMKII and Ca(2+)-activated Cl(-) channel activity to maintain contraction rate.The Journal of physiology · 2010Article
- Heart-specific deletion of CnB1 reveals multiple mechanisms whereby calcineurin regulates cardiac growth and function.The Journal of biological chemistry · 2010Article
- Vascular K ATP channels: dephosphorylation and deactivation.British journal of pharmacology · 2009Article
- Endothelium in pharmacology: 30 years on.British journal of pharmacology · 2009Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
background and purposeVascular ATP-sensitive potassium (K(ATP)) channels are activated by cyclic AMP elevating vasodilators through protein kinase A (PKA). Direct channel phosphorylation is a critical mechanism, though the phosphatase opposing these effects is unknown. Previously, we reported that calcineurin, a Ca(2+)-dependent phosphatase, inhibits K(ATP) channels, though neither the site nor the calcineurin isoform involved is established. Given that the type-2 regulatory (RII) subunit of PKA is a substrate for calcineurin we considered whether calcineurin regulates channel activity through interacting with PKA. EXPERIMENTAL APPROACH: Whole-cell recordings were made in HEK-293 cells stably expressing the vascular K(ATP) channel (K(IR)6.1/SUR2B). The effect of intracellular Ca(2+) and modulators of the calcineurin and PKA pathway on glibenclamide-sensitive currents were examined. KEY
resultsConstitutively active calcineurin A alpha but not A beta significantly attenuated K(ATP) currents activated by low intracellular Ca(2+), whereas calcineurin inhibitors had the opposite effect. PKA inhibitors reduced basal K(ATP) currents and responses to calcineurin inhibitors, consistent with the notion that some calcineurin action involves inhibition of PKA. However, raising intracellular Ca(2+) (equivalent to increasing calcineurin activity), almost completely inhibited K(ATP) channel activation induced by the catalytic subunit of PKA, whose enzymatic activity is independent of the RII subunit. In vitro phosphorylation experiments showed calcineurin could directly dephosphorylate a site in Kir6.1 that was previously phosphorylated by PKA. CONCLUSIONS AND IMPLICATIONS: Calcineurin A alpha regulates K(IR)6.1/SUR2B by inhibiting PKA-dependent phosphorylation of the channel as well as PKA itself. Such a mechanism is likely to directly oppose the action of vasodilators on the K(ATP) channel.
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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.