Long-chain acylcarnitines regulate the hERG channel
| Autor: | Pierre Fontanaud, François Labarthe, Aude Ouillé, Fabio Ferro, Patrick Bois, Dominique Babuty, T.A. Tran, Jean-Yves Le Guennec |
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| Přispěvatelé: | INSERM U921, Université de Tours, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Institut de physiologie et biologie cellulaires (IPBC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours) |
| Rok vydání: | 2012 |
| Předmět: |
Anatomy and Physiology
[SDV]Life Sciences [q-bio] Intracellular Space lcsh:Medicine 030204 cardiovascular system & hematology Pharmacology Mitochondrion Arrhythmias Cardiovascular Cardiovascular System Biochemistry Ion Channels Sudden cardiac death MESH: Dose-Response Relationship Drug 0302 clinical medicine lcsh:Science Membrane potential 0303 health sciences Multidisciplinary biology Chemistry MESH: Carnitine Fatty Acids Lipids Potassium channel 3. Good health Electrophysiology MESH: HEK293 Cells cardiovascular system MESH: Intracellular Space Medicine lipids (amino acids peptides and proteins) Long chain medicine.drug Research Article Computer Modeling MESH: Electrophysiological Processes hERG MESH: Ether-A-Go-Go Potassium Channels 03 medical and health sciences Carnitine medicine Humans cardiovascular diseases Biology 030304 developmental biology MESH: Humans Dose-Response Relationship Drug lcsh:R Proteins medicine.disease Ether-A-Go-Go Potassium Channels Electrophysiological Phenomena MESH: Extracellular Space HEK293 Cells Computer Science biology.protein lcsh:Q Extracellular Space |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2012, 7 (7), pp.e41686. ⟨10.1371/journal.pone.0041686⟩ PLoS ONE, Vol 7, Iss 7, p e41686 (2012) |
| ISSN: | 1932-6203 |
| Popis: | International audience; BACKGROUND AND PURPOSE: In some pathological conditions carnitine concentration is high while in others it is low. In both cases,cardiac arrhythmias can occur and lead to sudden cardiac death. It has been proposed that in ischaemia, acylcarnitine (acyl-CAR), but not carnitine, is involved in arrhythmias through modulation of ionic currents. We studied the effects of acyl-CARs on hERG, K(IR)2.1 and K(v)7.1/minK channels (channels responsible for I(KR), I(K1) and I(KS) respectively). EXPERIMENTAL APPROACH: HEK293 cells stably expressing hERG, K(IR)2.1 or Kv7.1/minK were studied using the patch clamp technique. Free carnitine (CAR) and acyl-CAR derivatives from medium- (C8 and C10) and long-chain (C16 and C18:1) fatty acids were applied intra- and extracellularly at different concentrations. For studies on hERG, C16 and C18:1 free fatty acid were also used. KEY RESULTS: Extracellular long-chain (LCAC), but not medium-chain, acyl-CAR,induced an increase of I(hERG) amplitude associated with a dose-dependent speeding of deactivation kinetics. They had no effect on K(IR)2.1 or Kv7.1/minK currents.Computer simulations of these effects were consistent with changes in action potential profile. CONCLUSIONS AND APPLICATIONS: Extracellular LCAC tonically regulates I(hERG) amplitude and kinetics under physiological conditions. This modulation may contribute to the changes in action potential duration that precede cardiac arrhythmias in ischaemia, diabetes and primary systemic carnitine deficiency. |
| Databáze: | OpenAIRE |
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