title: ATP-sensitive K+ channels in rat aorta and brain microvascular endothelial cells.
abstract: The endothelium plays an important role in the modulation of vascular tone and blood cell activation. Extensive work has demonstrated that the release of endothelium-derived relaxing factor (EDRF) from the endothelium is evoked by a number of physical and chemical stimuli requiring Ca2+. Because endothelial cells do not express voltage-dependent Ca2+ channels, Ca2+ influxes following receptor activation may be facilitated by cell hyperpolarizations mediated by the activation of K+ conductances. There has been recent interest in the role of ATP-sensitive K+ channels (KATP) suggesting that KATP may play a role in the regulation of blood flow. We have investigated the electrophysiological properties of an ATP-sensitive K+ conductance in whole cell and membrane patches from rat aorta and brain microvascular endothelial cells. Whole cell as well as single-channel currents were increased by either intracellular dialysis of ATP or application of glucose-free/NaCN (2 mM) solutions. Both currents were reversibly blocked by glibenclamide (1-100 microM). The KATP channel opener pinacidil (30 microM) caused activation of an outward current in the presence of physiological intracellular ATP concentrations. In inside-out patches, 10 microM-1 mM ATP invariably caused a dramatic decrease in channel activity. We conclude that both rat aorta and brain microvascular endothelial cells express KATP channels. KATP may play a role in the regulation of endothelial cell resting potential during impaired energy supply and therefore modulate EDRF release and thus cerebral blood flow.
authors.affiliation: Department of Neurological Surgery, University of Washington, Seattle 98104.
authors.forename: D
authors.initials: D
authors.lastname: Janigro
authors.forename: G A
authors.initials: GA
authors.lastname: West
authors.forename: E L
authors.initials: EL
authors.lastname: Gordon
authors.forename: H R
authors.initials: HR
authors.lastname: Winn
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D002474:Cell-Free System / Q000378:metabolism; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D008833:Microcirculation; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D051381:Rats
chemical_list: D006146:Guanidines; D015221:Potassium Channels; D020110:Pinacidil; D000255:Adenosine Triphosphate