External blockade of the major cardiac delayed-rectifier K+ channel (Kv1.5) by polyunsaturated fatty acids

Eric Honoré, Jacques Barhanin, Bernard Attali, Florian Lesage, Michel Lazdunski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The present work shows that arachidonic acid and some other long chain polyunsaturated fatty acids such as docosahexaenoic acid, which is abundant in fish oil, produce a direct open channel block of the major voltage- dependent K+ channel (Kv1.5) cloned in cardiac cells. The inhibitory action of these selected fatty acids is seen when they are applied extracellularly but not when they are included in the patch pipette. Fatty acids then appear to bind to an external site on the Kv1.5 channel structure. Inhibition of Kv1.5 channel activity by polyunsaturated fatty acids (acceleration of the apparent inactivation and decrease of the peak current) is similar to that produced by the class III antiarrhythmic tedisamil. Docosahexaenoic acid and arachidonic acid also inhibit the delayed-rectifier K+ channel currents in cultured mouse and rat cardiomyocytes. These results are discussed in the light of the reported fatty acids effects on cardiac function in diseased states. Since Kv1.5 is also present in the brain, the results reported here could also have a significance in terms of processes such as long-term potentiation or depression.

Original languageEnglish
Pages (from-to)1937-1941
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number5
DOIs
StatePublished - 1 Mar 1994
Externally publishedYes

Keywords

  • K conductance
  • antiarrhythmics
  • arachidonic acid
  • fish oil
  • tedisamil

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