title: Uncoupling of neurovascular communication after transient global cerebral ischemia is caused by impaired parenchymal smooth muscle Kir channel function.
abstract: Transient global cerebral ischemia is often followed by delayed disturbances of cerebral blood flow, contributing to neuronal injury. The pathophysiological processes underlying such disturbances are incompletely understood. Here, using an established model of transient global cerebral ischemia, we identify dramatically impaired neurovascular coupling following ischemia. This impairment results from the loss of functional inward rectifier potassium (KIR) channels in the smooth muscle of parenchymal arterioles. Therapeutic strategies aimed at protecting or restoring cerebrovascular KIR channel function may therefore improve outcomes following ischemia.
authors.affiliation: Department of Pharmacology, College of Medicine, University of Vermont, Burlington, Vermont, USA Department of Clinical Experimental Research, Glostrup Research Institute, Glostrup University Hospital, Glostrup, Denmark.
authors.forename: Gro Klitgaard
authors.initials: GK
authors.lastname: Povlsen
authors.affiliation: Department of Pharmacology, College of Medicine, University of Vermont, Burlington, Vermont, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Longden
authors.affiliation: Department of Pharmacology, College of Medicine, University of Vermont, Burlington, Vermont, USA.
authors.forename: Adrian D
authors.initials: AD
authors.lastname: Bonev
authors.forename: David C
authors.initials: DC
authors.lastname: Hill-Eubanks
authors.affiliation: Department of Pharmacology, College of Medicine, University of Vermont, Burlington, Vermont, USA Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK mark.nelson@uvm.edu.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Nelson
mesh_terms: D000818:Animals; D001160:Arterioles / Q000378:metabolism* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D004730:Endothelium, Vascular; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000503:physiopathology; D000069336:Neurovascular Coupling / Q000502:physiology*; D000072356:Parenchymal Tissue / Q000098:blood supply*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D017207:Rats, Sprague-Dawley
chemical_list: D024661:Potassium Channels, Inwardly Rectifying
keywords: KIR channel; Neurovascular coupling; cerebral blood flow; ischemia; smooth muscle