Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 285, Issue 4, Pages H1590-H1599Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00376.2003
Keywords
calcium; brain; purinergic; small conductance potassium channels; large conductance potassium channels; endothelium-derived hyperpolarizing factor
Funding
- NINDS NIH HHS [R01-NS-37250, P01-NS-27616] Funding Source: Medline
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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 mul/min). Artery diameter was measured simultaneously with either endothelial intracellular Ca2+ concentration ([Ca2+](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 K-Ca 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 [Ca2+](i). We conclude that the mechanism of EDHF-mediated dilations in cerebral arteries requires stimulation of endothelial IKCa channels to promote endothelial hyperpolarization and subsequent vasodilatation.
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