ArticleProceedings of the National Academy of Sciences of the United States of America1997
Phentolamine block of KATP channels is mediated by Kir6.2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 149 citations in OpenAlex.
- β-Adrenergic Blockers Increase cAMP and Stimulate Insulin Secretion Through a PKA/RYR2/TRPM5 Pathway in Pancreatic β-Cells In Vitro.Pharmacology research & perspectives · 2025Article
- Molecular Modeling, Synthesis, and Antihyperglycemic Activity of the New Benzimidazole Derivatives - Imidazoline Receptor Agonists.Drug design, development and therapy · 2024Article
- Inward and outward currents of native and cloned K(ATP) channels (Kir6.2/SUR1) share single-channel kinetic properties.Biochemistry and biophysics reports · 2022Article
- An Imidazoline 2 Receptor Ligand Relaxes Mouse AortaFrontiers in pharmacology · 2022Article
- Kir Channel Molecular Physiology, Pharmacology, and Therapeutic Implications.Handbook of experimental pharmacology · 2021Review
- Evidence that the multiflorine-derived substituted quinazolidine 55P0251 augments insulin secretion and lowers blood glucose via antagonism at αDiabetes, obesity & metabolism · 2020Article
- Insulin Release Mechanism Modulated by Toxins Isolated from Animal Venoms: From Basic Research to Drug Development Prospects.Molecules (Basel, Switzerland) · 2019Review
- Lipophilicity predicts the ability of nonsulphonylurea drugs to block pancreatic beta-cell KEndocrinology, diabetes & metabolism · 2018Article
- Running out of time: the decline of channel activity and nucleotide activation in adenosine triphosphate-sensitive K-channels.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2016Review
- Pharmacogenomics of cardiovascular complications in diabetes and obesity.Recent patents on biotechnology · 2014Review
- Mechanisms of antihyperglycaemic action of efaroxan in mice: time for reappraisal of α2A-adrenergic antagonism in the treatment of type 2 diabetes?Diabetologia · 2012Article
- Novel IJournal of diabetes & metabolism · 2012Article
- Do insulinotropic glucose-lowering drugs do more harm than good? The hypersecretion hypothesis revisited.Diabetologia · 2010Article
- Pharmacological stimulation and inhibition of insulin secretion in mouse islets lacking ATP-sensitive K+ channels.British journal of pharmacology · 2010Article
- An in-frame deletion in Kir6.2 (KCNJ11) causing neonatal diabetes reveals a site of interaction between Kir6.2 and SUR1.The Journal of clinical endocrinology and metabolism · 2009Article
- Review. SUR1: a unique ATP-binding cassette protein that functions as an ion channel regulator.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2009Review
- A new benzoxazine compound blocks KATP channels in pancreatic beta cells: molecular basis for tissue selectivity in vitro and hypoglycaemic action in vivo.British journal of pharmacology · 2006Article
- Article
- Modeling regulation of cardiac KATP and L-type Ca2+ currents by ATP, ADP, and Mg2+.Biophysical journal · 2005Article
- Inhibition of ATP-sensitive potassium channels by haloperidol.British journal of pharmacology · 2004Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
Abstract
The ATP-sensitive K+-channel (KATP channel) plays a key role in insulin secretion from pancreatic beta cells. It is closed both by glucose metabolism and the sulfonylurea drugs that are used in the treatment of noninsulin-dependent diabetes mellitus, thereby initiating a membrane depolarization that activates voltage-dependent Ca2+ entry and insulin release. The beta cell KATP channel is a complex of two proteins: Kir6.2 and SUR1. The former is an ATP-sensitive K+-selective pore, whereas SUR1 is a channel regulator that endows Kir6.2 with sensitivity to sulfonylureas. A number of drugs containing an imidazoline moiety, such as phentolamine, also act as potent stimulators of insulin secretion, but their mechanism of action is unknown. We have used a truncated form of Kir6.2, which expresses independently of SUR1, to show that phentolamine does not inhibit KATP channels by interacting with SUR1. Instead, our results argue that phentolamine may interact directly with Kir6.2 to produce a voltage-independent reduction in channel activity. The single-channel conductance is unaffected. Although the ATP molecule also contains an imidazoline group, the site at which phentolamine blocks is not identical to the ATP-inhibitory site, because phentolamine block of an ATP-insensitive mutant (K185Q) is normal. KATP channels also are found in the heart where they are involved in the response to cardiac ischemia: they also are blocked by phentolamine. Our results suggest that this may be because Kir6.2, which is expressed in the heart, forms the pore of the cardiac KATP 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.