title: KIRchannels tune electrical communication in cerebral arteries.
abstract: The conducted vasomotor response reflects electrical communication in the arterial wall and the distance signals spread is regulated by three factors including resident ion channels. This study defined the role of inward-rectifying K+channels (KIR) in governing electrical communication along hamster cerebral arteries. Focal KCl application induced a vasoconstriction that conducted robustly, indicative of electrical communication among cells. Inhibiting dominant K+conductances had no attenuating effect, the exception being Ba2+blockade of KIR. Electrophysiology and Q-PCR analysis of smooth muscle cells revealed a Ba2+-sensitive KIRcurrent comprised of KIR2.1/2.2 subunits. This current was surprisingly small and when incorporated into a model, failed to account for the observed changes in conduction. We theorized a second population of KIRchannels exist and consistent with this idea, a robust Ba2+-sensitive KIR2.1/2.2 current was observed in endothelial cells. When both KIRcurrents were incorporated into, and then inhibited in our model, conduction decay was substantive, aligning with experiments. Enhanced decay was ascribed to the rightward shift in membrane potential and the increased feedback arising from voltage-dependent-K+channels. In summary, this study shows that two KIRpopulations work collaboratively to govern electrical communication and the spread of vasomotor responses along cerebral arteries.
authors.affiliation: 1 Department of Physiology and Pharmacology, University of Western Ontario, London, Canada.|2 Department of Physiology and Pharmacology, Hotchkiss Brain Institute, Libin Cardiovascular Institute, University of Calgary, Calgary, Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: Sancho
authors.affiliation: 2 Department of Physiology and Pharmacology, Hotchkiss Brain Institute, Libin Cardiovascular Institute, University of Calgary, Calgary, Canada.
authors.forename: Nina C
authors.initials: NC
authors.lastname: Samson
authors.affiliation: 3 Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Bjorn O
authors.initials: BO
authors.lastname: Hald
authors.affiliation: 2 Department of Physiology and Pharmacology, Hotchkiss Brain Institute, Libin Cardiovascular Institute, University of Calgary, Calgary, Canada.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Hashad
authors.affiliation: 4 Department of Anesthesiology, Baylor College of Medicine, Houston, USA.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Marrelli
authors.affiliation: 1 Department of Physiology and Pharmacology, University of Western Ontario, London, Canada.|2 Department of Physiology and Pharmacology, Hotchkiss Brain Institute, Libin Cardiovascular Institute, University of Calgary, Calgary, Canada.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Brett
authors.affiliation: 1 Department of Physiology and Pharmacology, University of Western Ontario, London, Canada.|2 Department of Physiology and Pharmacology, Hotchkiss Brain Institute, Libin Cardiovascular Institute, University of Calgary, Calgary, Canada.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Welsh
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002536:Cerebral Arteries / Q000378:metabolism* / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008647:Mesocricetus; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000502:physiology; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D012039:Regional Blood Flow / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D024661:Potassium Channels, Inwardly Rectifying; D011189:Potassium Chloride
keywords: Electrophysiology; endothelium; microcirculation; potassium channels; smooth muscle