title: Long-chain acylcarnitines regulate the hERG channel.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  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.
authors: INSERM U921, Université François-Rabelais, Tours, France.
authors: Fabio
authors: F
authors: Ferro
authors: Aude
authors: A
authors: Ouillé
authors: Truong-An
authors: TA
authors: Tran
authors: Pierre
authors: P
authors: Fontanaud
authors: Patrick
authors: P
authors: Bois
authors: Dominique
authors: D
authors: Babuty
authors: François
authors: F
authors: Labarthe
authors: Jean-Yves
authors: JY
authors: Le Guennec
mesh_terms: D002331:Carnitine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D055724:Electrophysiological Phenomena / Q000187:drug effects; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; C116917:acylcarnitine; D002331:Carnitine