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Long-Chain Acylcarnitines Regulate the hERG Channel
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Long-Chain Acylcarnitines Regulate the hERG Channel
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Journal Article
Long-Chain Acylcarnitines Regulate the hERG Channel
2012
Overview
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).
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.
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.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Biology
/ Carnitine - analogs & derivatives
/ Chains
/ Diabetes
/ Dose-Response Relationship, Drug
/ Electrophysiological Phenomena - drug effects
/ Electrophysiological Processes
/ Ether-A-Go-Go Potassium Channels
/ Ether-A-Go-Go Potassium Channels - metabolism
/ Extracellular Space - drug effects
/ Extracellular Space - metabolism
/ Heart
/ Humans
/ Intracellular Space - drug effects
/ Intracellular Space - metabolism
/ Ischemia
/ Kinetics
/ Medicine
/ Mutation
/ Potassium channels (inwardly-rectifying)
/ Potassium channels (voltage-gated)
/ Rodents
