K+ current inhibition by amphiphilic fatty acid metabolites in rat ventricular myocytes

Zhi Xu, George J. Rozanski

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Fatty acid metabolites accumulate in the heart under pathophysiological conditions that affect β-oxidation and can elicit marked electrophysiological changes that are arrhythmogenic. The purpose of the present study was to determine the impact of amphiphilic fatty acid metabolites on K+ currents that control cardiac refractoriness and excitability. Transient outward (I(to)) and inward rectifier (I(K1)) K+ currents were recorded by the whole cell Voltage-clamp technique in rat ventricular myocytes, and the effects of two major fatty acid metabolites were examined: palmitoylcarnitine and palmitoyl-coenzyme A (palmitoyl-CoA). Palmitoylcarnitine (0.5-10 μM) caused a concentration-dependent decrease in I(to) density in myocytes internally dialyzed with the amphiphile; 10 μM reduced mean I(to) density at +60 mV by 62% compared with control (P < 0.05). In contrast, external palmitoylcarnitine at the same concentrations had no effect, nor did internal dialysis significantly alter I(K1). Dialysis with palmitoyl-CoA (1-10 μM) produced a smaller decrease in I(to) density compared with that produced by palmitoylcarnitine; 10 μM reduced mean I(to) density at +60 mV by 37% compared with control (P < 0.05). Both metabolites delayed recovery of I(to) from inactivation but did not affect voltage- dependent properties. Moreover, the effects of palmitoylcarnitine were relatively specific, as neither palmitate (10 μM) nor carnitine (10 μM) alone significantly influenced I(to) when added to the pipette solution. These data therefore suggest that amphiphilic fatty acid metabolites downregulate I(to) channels by a mechanism confined to the cytoplasmic side of the membrane. This decrease in cardiac K+ channel activity may delay repolarization under pathophysiological conditions in which amphiphile accumulation is postulated to occur, such as diabetes mellitus or myocardial infarction.

Original languageEnglish (US)
Pages (from-to)C1660-C1667
JournalAmerican Journal of Physiology - Cell Physiology
Volume275
Issue number6 44-6
DOIs
StatePublished - 1998

Keywords

  • Fatty acids
  • Heart
  • Potassium channels
  • Transient outward current

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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