20-HETE is an endogenous inhibitor of the large-conductance Ca2+-activated K+ channel in renal arterioles

Ai Ping Zou, John T. Fleming, John R. Falck, Elizabeth R. Jacobs, Debebe Gebremedhin, David R. Harder, Richard J. Roman

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263 Scopus citations

Abstract

The present study examined the effects of 20-hydroxyeicosatetraenoic acid (20-HETE) and 17-octadecynoic acid (17-ODYA), an inhibitor of the metabolism of arachidonic acid by P-450, on K+-channel activity in vascular smooth muscle cells (VSM) isolated from renal arterioles of the rat. Two types of K+ channels were characterized using inside-out excised membrane patches. One channel exhibited a large conductance (250.3 ± 5 pS), was activated by membrane depolarization and elevations in cytoplasmic Ca2+ concentration, and was blocked by low concentrations (<1 mM) of tetraethylammonium (TEA). The other K+ channel exhibited an intermediate conductance (46.3 ± 3 pS), was activated by membrane depolarization but not by changes in intracellular Ca2+ concentration, and was blocked by 4-aminopyridine (5 mM). Addition of 20-HETE to the bath (1-100 nM), reduced the frequency of opening of the large-conductance Ca2+-activated K+ channel recorded using cell-attached patches on VSM. It had no effect on the intermediate-conductance K+ channel. 17-ODYA (1 μM) increased the activity of the large-conductance Ca2+-activated K+ channel, and this effect was reversed by 20-HETE (10 nM). 20-HETE (1-1000 nM) reduced the diameter of isolated perfused small renal arteries of the rat by ∼15%. TEA (1 mM) blocked the vasoconstrictor response to 20-HETE (100 nM). These studies suggest that 20-HETE is an endogenously formed vasoconstrictor that acts in part by inhibiting the opening of the large-conductance Ca2+-activated K+ channel in renal arteriolar VSM.

Original languageEnglish (US)
Pages (from-to)R228-R237
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume270
Issue number1 39-1
DOIs
StatePublished - 1996

Keywords

  • Cytochrome P-450
  • Eicosanoids
  • Kidney
  • Patch clamp
  • Renal artery

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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