ArticleProceedings of the National Academy of Sciences of the United States of America1999
Pharmacological plasticity of cardiac ATP-sensitive potassium channels toward diazoxide revealed by ADP.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 180 citations in OpenAlex.
- Acute Metabolic Stress Induces Lymphatic Dysfunction Through KATP Channel Activation.Function (Oxford, England) · 2024Article
- Exploring the Pathophysiology of ATP-Dependent Potassium Channels in Insulin Resistance.International journal of molecular sciences · 2024Review
- Article
- Pulmonary hypertension associated with diazoxide: the SUR1 paradox.ERJ open research · 2023Review
- The Pharmacology of ATP-Sensitive KHandbook of experimental pharmacology · 2021Article
- TRPM4 channel inhibitors 9-phenanthrol and glibenclamide differentially decrease guinea pig detrusor smooth muscle whole-cell cation currents and phasic contractions.American journal of physiology. Cell physiology · 2020Article
- Possible New Strategies for the Treatment of Congenital Hyperinsulinism.Frontiers in endocrinology · 2020Article
- Structure-Activity Relationships, Pharmacokinetics, and Pharmacodynamics of the Kir6.2/SUR1-Specific Channel Opener VU0071063.The Journal of pharmacology and experimental therapeutics · 2019Article
- Ischemia Reperfusion Injury Produces, and Ischemic Preconditioning Prevents, Rat Cardiac Fibroblast Differentiation: Role of KJournal of cardiovascular development and disease · 2019Article
- The shifting landscape of KATP channelopathies and the need for 'sharper' therapeutics.Future medicinal chemistry · 2016Review
- KATP Channels in the Cardiovascular System.Physiological reviews · 2016Review
- Isosteviol Sensitizes sarcKATP Channels towards Pinacidil and Potentiates Mitochondrial Uncoupling of Diazoxide in Guinea Pig Ventricular Myocytes.Oxidative medicine and cellular longevity · 2016Article
- Kir6.2 activation by sulfonylurea receptors: a different mechanism of action for SUR1 and SUR2A subunits via the same residues.Physiological reports · 2015Article
- Molecular determinants of ATP-sensitive potassium channel MgATPase activity: diabetes risk variants and diazoxide sensitivity.Bioscience reports · 2015Article
- The unusual stoichiometry of ADP activation of the KATP channel.Frontiers in physiology · 2014Article
- Multiplicity of effectors of the cardioprotective agent, diazoxide.Pharmacology & therapeutics · 2013Review
- Functional roles of KATP channel subunits in metabolic inhibition.Journal of molecular and cellular cardiology · 2013Article
- A new pROM king for the mitoK(ATP) dance: ROMK takes the lead.Circulation research · 2012Article
- The mitochondrial K(ATP) channel--fact or fiction?Journal of molecular and cellular cardiology · 2012Article
- Effects of KATP channel openers diazoxide and pinacidil in coronary-perfused atria and ventricles from failing and non-failing human hearts.Journal of molecular and cellular cardiology · 2011Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pharmacological phenotype of ATP-sensitive potassium (K(ATP)) channels is defined by their tissue-specific regulatory subunit, the sulfonylurea receptor (SUR), which associates with the pore-forming channel core, Kir6.2. The potassium channel opener diazoxide has hyperglycemic and hypotensive properties that stem from its ability to open K(ATP) channels in pancreas and smooth muscle. Diazoxide is believed not to have any significant action on cardiac sarcolemmal K(ATP) channels. Yet, diazoxide can be cardioprotective in ischemia and has been found to bind to the presumed cardiac sarcolemmal K(ATP) channel-regulatory subunit, SUR2A. Here, in excised patches, diazoxide (300 microM) activated pancreatic SUR1/Kir6.2 currents and had little effect on native or recombinant cardiac SUR2A/Kir6.2 currents. However, in the presence of cytoplasmic ADP (100 microM), SUR2A/Kir6.2 channels became as sensitive to diazoxide as SUR1/Kir6. 2 channels. This effect involved specific interactions between MgADP and SUR, as it required Mg(2+), but not ATP, and was abolished by point mutations in the second nucleotide-binding domain of SUR, which impaired channel activation by MgADP. At the whole-cell level, in cardiomyocytes treated with oligomycin to block mitochondrial function, diazoxide could also activate K(ATP) currents only after cytosolic ADP had been raised by a creatine kinase inhibitor. Thus, ADP serves as a cofactor to define the responsiveness of cardiac K(ATP) channels toward diazoxide. The present demonstration of a pharmacological plasticity of K(ATP) channels identifies a mechanism for the control of channel activity in cardiac cells depending on the cellular ADP levels, which are elevated under ischemia.
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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.