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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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)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume270
Issue number1 39-1
StatePublished - 1996

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Calcium-Activated Potassium Channels
Arterioles
Kidney
Vascular Smooth Muscle
Smooth Muscle Myocytes
Tetraethylammonium
Vasoconstrictor Agents
Membranes
4-Aminopyridine
Renal Artery
Baths
Arachidonic Acid
20-hydroxy-5,8,11,14-eicosatetraenoic acid

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

20-HETE is an endogenous inhibitor of the large-conductance Ca2+-activated K+ channel in renal arterioles. / Zou, Ai Ping; Fleming, John T.; Falck, John R.; Jacobs, Elizabeth R.; Gebremedhin, Debebe; Harder, David R.; Roman, Richard J.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 270, No. 1 39-1, 1996.

Research output: Contribution to journalArticle

Zou, Ai Ping ; Fleming, John T. ; Falck, John R. ; Jacobs, Elizabeth R. ; Gebremedhin, Debebe ; Harder, David R. ; Roman, Richard J. / 20-HETE is an endogenous inhibitor of the large-conductance Ca2+-activated K+ channel in renal arterioles. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 1996 ; Vol. 270, No. 1 39-1.
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T1 - 20-HETE is an endogenous inhibitor of the large-conductance Ca2+-activated K+ channel in renal arterioles

AU - Zou, Ai Ping

AU - Fleming, John T.

AU - Falck, John R.

AU - Jacobs, Elizabeth R.

AU - Gebremedhin, Debebe

AU - Harder, David R.

AU - Roman, Richard J.

PY - 1996

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AB - 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.

KW - Cytochrome P-450

KW - Eicosanoids

KW - Kidney

KW - Patch clamp

KW - Renal artery

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