ArticleThe Journal of physiology2006
Cytoplasmic accumulation of long-chain coenzyme A esters activates KATP and inhibits Kir2.1 channels.
Article in The Journal of physiology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Inhibition of lipolysis in visceral adipose tissue from obese mice and humans prevents impairment of endothelial Kir2.1 channels.Channels (Austin, Tex.) · 2025Article
- Visceral adipose of obese mice inhibits endothelial inwardly rectifying KAmerican journal of physiology. Cell physiology · 2024Article
- Structural basis of the activation of TRPV5 channels by long-chain acyl-Coenzyme-A.Nature communications · 2023Article
- The versatile regulation of K2P channels by polyanionic lipids of the phosphoinositide and fatty acid metabolism.The Journal of general physiology · 2022Article
- Targeting Lipid-Ion Channel Interactions in Cardiovascular Disease.Frontiers in cardiovascular medicine · 2022Article
- Comparison of KHandbook of experimental pharmacology · 2021Article
- Kir Channel Molecular Physiology, Pharmacology, and Therapeutic Implications.Handbook of experimental pharmacology · 2021Review
- Palmitoylation of the KProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Loss of ACOT7 potentiates seizures and metabolic dysfunction.American journal of physiology. Endocrinology and metabolism · 2019Article
- A systems biology approach towards the identification of candidate therapeutic genes and potential biomarkers for Parkinson's disease.PloS one · 2019Article
- Lipid signaling to membrane proteins: From second messengers to membrane domains and adapter-free endocytosis.The Journal of general physiology · 2018Review
- Phosphoinositide regulation of TRPV1 revisited.Pflugers Archiv : European journal of physiology · 2015Review
- Massive palmitoylation-dependent endocytosis during reoxygenation of anoxic cardiac muscle.eLife · 2013Article
- Acute regional left atrial ischemia causes acceleration of atrial drivers during atrial fibrillation.Heart rhythm · 2013Article
- Acyl coenzyme A thioesterase 7 regulates neuronal fatty acid metabolism to prevent neurotoxicity.Molecular and cellular biology · 2013Article
- Characteristics and mechanisms of hypothalamic neuronal fatty acid sensing.American journal of physiology. Regulatory, integrative and comparative physiology · 2009Article
- How highly charged anionic lipids bind and regulate ion channels.The Journal of general physiology · 2008Review
- Article
- Dual control of cardiac Na+ Ca2+ exchange by PIP(2): electrophysiological analysis of direct and indirect mechanisms.The Journal of physiology · 2007Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Long-chain fatty acids acyl coenzyme A esters (LC-CoA) are obligate intermediates of fatty acid metabolism and have been shown to activate K(ATP) channels but to inhibit most other Kir channels (e.g. Kir2.1) by direct channel binding. The activation of K(ATP) channels by elevated levels of LC-CoA may be involved in the pathophysiology of type 2 diabetes, the hypothalamic sensing of circulating fatty acids and the regulation of cardiac K(ATP) channels. However, LC-CoA are effectively buffered in the cytoplasm and it is currently not clear whether their free concentration can reach levels sufficient to affect Kir channels in vivo. Here, we report that extracellular oleic acid complexed with albumin at an unbound concentration of 81 +/- 1 nm strongly activated K(ATP) channels and inhibited Kir2.1 channels in Chinese hamster ovary (CHO) cells as well as endogenous Kir currents in human embryonic kidney (HEK293) cells. These effects were only seen in the presence of a high concentration of glucose (25 mm), a condition known to promote the accumulation of LC-CoA by inhibiting their mitochondrial uptake via carnitine-palmitoyl-transferase-1 (CPT1). Accordingly, pharmacological inhibition of CPT1 by etomoxir restored the effects of oleic acid under low glucose conditions. Finally, triacsin C, an inhibitor of the acyl-CoA synthetase, which is necessary for LC-CoA formation, abolished the effects of extracellular oleic acid on the various Kir channels. These results establish the direct regulation of Kir channels by the cytoplasmic accumulation of LC-CoA, which might be of physiological and pathophysiological relevance in a variety of tissues.
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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.