Inhibition of endothelium-dependent vasorelaxation by extracellular K +: A novel controlling signal for vascular contractility

Geun Hee Seol, Seung Cheol Ahn, Ji Aee Kim, Bernd Nilius, Suk Hyo Suh

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The effects of extracellular K+ on endothelium-dependent relaxation (EDR) and on intracellular Ca2+ concentration ([Ca 2+]i) were examined in mouse aorta, mouse aorta endothelial cells (MAEC), and human umbilical vein endothelial cells (HUVEC). In mouse aortic rings precontracted with prostaglandin F or norepinephrine, an increase in extracellular K+ concentration ([K+]o) from 6 to 12 mM inhibited EDR concentration dependently. In endothelial cells, an increase in [K+]o inhibited the agonist-induced [Ca2+]i increase concentration dependently. Similar to K+, Cs+ also inhibited EDR and the increase in [Ca2+]i concentration dependently. In current-clamped HUVEC, increasing [K+]o from 6 to 12 mM depolarized membrane potential from -32.8 ± 2.7 to -8.6 ± 4.9 mV (n = 8). In voltage-clamped HUVEC, depolarizing the holding potential from -50 to -25 mV decreased [Ca2+]i significantly from 0.95 ± 0.03 to 0.88 ± 0.03 μM (n = 11, P < 0.01) and further decreased [Ca2+]i, to 0.47 ± 0.04 μM by depolarizing the holding potential from -25 to 0 mV (n = 11, P < 0.001). Tetraethylammonium (1 mM) inhibited EDR and the ATP-induced [Ca2+]i increase in voltage-clamped MAEC. The intermediate-conductance Ca2+-activated K+ channel openers 1-ethyl-2-benzimidazolinone, chlorozoxazone, and zoxazolamine reversed the K+-induced inhibition of EDR and increase in [Ca 2+]i. The K+-induced inhibition of EDR and increase in [Ca2+]i was abolished by the Na +-K+ pump inhibitor ouabain (10 μM). These results indicate that an increase of [K+]o in the physiological range (6-12 mM) inhibits [Ca2+]i increase in endothelial cells and diminishes EDR by depolarizing the membrane potential, decreasing K+ efflux, and activating the Na+-K+ pump, thereby modulating the release of endothelium-derived vasoactive factors from endothelial cells and vasomotor tone.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number1 55-1
Publication statusPublished - 2004 Jan 1
Externally publishedYes



  • Endothelial cell
  • Intracellular calcium

ASJC Scopus subject areas

  • Physiology

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