Role of endothelial intermediate conductance KCa channels in cerebral EDHF-mediated dilations

Sean P. Marrelli, Maxim S. Eckmann, Michael S. Hunte

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

The present study evaluated the role of endothelial intermediate conductance calcium-sensitive potassium channels (IKCa) in the mechanism of endothelium-derived hyperpolarizing factor (EDHF)-mediated dilations in pressurized cerebral arteries. Male rat middle cerebral arteries (MCA) were mounted in an isolated vessel chamber, pressurized (85 mmHg), and luminally perfused (100 μl/min). Artery diameter was measured simultaneously with either endothelial intracellular Ca2+ concentration ([Ca 2+]i; fura-2) or changes in endothelial membrane potential [4-{2-{6-(dioctylamino)-2-naphthalenyl]ethenyl}1-(3-sulfopropyl)-pyridinium (di-8-ANEPPS)]. Nitric oxide synthase and cyclooxygenase inhibitors were present throughout. Luminal application of UTP produced EDHF-mediated dilations that correlated with significant endothelial hyperpolarization. The dilation and endothelial hyperpolarization were virtually abolished by inhibitors of IKCa channels but not by selective inhibitors of small or large conductance KCa channels (apamin and iberiotoxin, respectively). Additionally, direct stimulation of endothelial IKCa channels with 1-ethyl-2-benzimidazolinone (1-EBIO) produced endothelial hyperpolarization and vasodilatation that were blocked by inhibitors of IKCa channels. 1-EBIO hyperpolarized the endothelium but did not affect endothelial [Ca 2+]i. We conclude that the mechanism of EDHF-mediated dilations in cerebral arteries requires stimulation of endothelial IK Ca channels to promote endothelial hyperpolarization and subsequent vasodilatation.

Original languageEnglish (US)
Pages (from-to)H1590-H1599
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number4 54-4
DOIs
StatePublished - Oct 1 2003
Externally publishedYes

Keywords

  • Brain
  • Calcium
  • Endothelium-derived hyperpolarizing factor
  • Large conductance potassium channels
  • Purinergic
  • Small conductance potassium channels

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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