title: Role of endothelial intermediate conductance KCa channels in cerebral EDHF-mediated dilations.
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 microl/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 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 [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.
authors.affiliation: Baylor College of Medicine, Department of Anesthesiology, One Baylor Plaza, Suite 434-D, Houston, TX 77030, USA. marrelli@bcm.tmc.edu
authors.forename: Sean P
authors.initials: SP
authors.lastname: Marrelli
authors.forename: Maxim S
authors.initials: MS
authors.lastname: Eckmann
authors.forename: Michael S
authors.initials: MS
authors.lastname: Hunte
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009994:Osmolar Concentration; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000502:physiology*; D011312:Pressure; D011726:Pyridinium Compounds; D051381:Rats; D020318:Rats, Long-Evans; D014664:Vasodilation / Q000502:physiology*
chemical_list: C089669:1-(3-sulfonatopropyl)-4-(beta-(2-(di-n-octylamino)-6-naphthyl)vinyl)pyridinium betaine; D001562:Benzimidazoles; D001685:Biological Factors; D002120:Calcium Channel Agonists; D005456:Fluorescent Dyes; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D011726:Pyridinium Compounds; C067410:endothelium-dependent hyperpolarization factor; C102635:1-ethyl-2-benzimidazolinone; D002118:Calcium