title: Requisite Role of Kv1.5 Channels in Coronary Metabolic Dilation.
abstract: BACKGROUND
  In the working heart, coronary blood flow is linked to the production of metabolites, which modulate tone of smooth muscle in a redox-dependent manner. Voltage-gated potassium channels (Kv), which play a role in controlling membrane potential in vascular smooth muscle, have certain members that are redox-sensitive.
  
  
  OBJECTIVE
  To determine the role of redox-sensitive Kv1.5 channels in coronary metabolic flow regulation.
  
  
  RESULTS
  In mice (wild-type [WT], Kv1.5 null [Kv1.5(-/-)], and Kv1.5(-/-) and WT with inducible, smooth muscle-specific expression of Kv1.5 channels), we measured mean arterial pressure, myocardial blood flow, myocardial tissue oxygen tension, and ejection fraction before and after inducing cardiac stress with norepinephrine. Cardiac work was estimated as the product of mean arterial pressure and heart rate. Isolated arteries were studied to establish whether genetic alterations modified vascular reactivity. Despite higher levels of cardiac work in the Kv1.5(-/-) mice (versus WT mice at baseline and all doses of norepinephrine), myocardial blood flow was lower in Kv1.5(-/-) mice than in WT mice. At high levels of cardiac work, tissue oxygen tension dropped significantly along with ejection fraction. Expression of Kv1.5 channels in smooth muscle in the null background rescued this phenotype of impaired metabolic dilation. In isolated vessels from Kv1.5(-/-) mice, relaxation to H2O2 was impaired, but responses to adenosine and acetylcholine were normal compared with those from WT mice.
  
  
  CONCLUSIONS
  Kv1.5 channels in vascular smooth muscle play a critical role in coupling myocardial blood flow to cardiac metabolism. Absence of these channels disassociates metabolism from flow, resulting in cardiac pump dysfunction and tissue hypoxia.
authors.affiliation: Department of Integrative Medical Sciences.
authors.forename: Vahagn
authors.initials: V
authors.lastname: Ohanyan
authors.affiliation: Department of Integrative Medical Sciences.
authors.forename: Liya
authors.initials: L
authors.lastname: Yin
authors.affiliation: Departement Internal Medicine, Canton Medical Education Foundation.
authors.forename: Raffi
authors.initials: R
authors.lastname: Bardakjian
authors.affiliation: Department of Integrative Medical Sciences.
authors.forename: Christopher
authors.initials: C
authors.lastname: Kolz
authors.affiliation: Department of Integrative Medical Sciences.
authors.forename: Molly
authors.initials: M
authors.lastname: Enrick
authors.affiliation: Department of Integrative Medical Sciences.
authors.forename: Tatevik
authors.initials: T
authors.lastname: Hakobyan
authors.affiliation: Department of Integrative Medical Sciences.
authors.forename: John
authors.initials: J
authors.lastname: Kmetz
authors.affiliation: Department of Integrative Medical Sciences.
authors.forename: Ian
authors.initials: I
authors.lastname: Bratz
authors.affiliation: Department of Integrative Medical Sciences.
authors.forename: Jordan
authors.initials: J
authors.lastname: Luli
authors.affiliation: Department of Radiology and Medicine, Geisel School of Medicine at Dartmouth College.
authors.forename: Masaki
authors.initials: M
authors.lastname: Nagane
authors.affiliation: Department of Radiology and Medicine, Geisel School of Medicine at Dartmouth College.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Khan
authors.affiliation: Department of Radiology and Medicine, Geisel School of Medicine at Dartmouth College.
authors.forename: Huagang
authors.initials: H
authors.lastname: Hou
authors.affiliation: Department of Radiology and Medicine, Geisel School of Medicine at Dartmouth College.
authors.forename: Periannan
authors.initials: P
authors.lastname: Kuppusamy
authors.affiliation: Department of Integrative Medical Sciences.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Graham
authors.affiliation: Department of Integrative Medical Sciences.
authors.forename: Frances Kwan
authors.initials: FK
authors.lastname: Fu
authors.affiliation: Department of Integrative Medical Sciences.
authors.forename: Danielle
authors.initials: D
authors.lastname: Janota
authors.affiliation: Department of Pharmaceutical Sciences, Northeast Ohio Medical University.
authors.forename: Moses O
authors.initials: MO
authors.lastname: Oyewumi
authors.affiliation: Department of Integrative Medical Sciences.
authors.forename: Suzanna
authors.initials: S
authors.lastname: Logan
authors.affiliation: Division of Cardiovascular Medicine, UHN62, Oregon Health and Science University.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Lindner
authors.affiliation: Department of Integrative Medical Sciences.
authors.forename: William M
authors.initials: WM
authors.lastname: Chilian
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000502:physiology*; D003331:Coronary Vessels / Q000378:metabolism*; D051666:Kv1.5 Potassium Channel / Q000502:physiology*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D014664:Vasodilation / Q000502:physiology*
chemical_list: D051666:Kv1.5 Potassium Channel
keywords: cardiac function; contrast echocardiography; hydrogen peroxide; ion channel; transgenic mice; vasodilation; voltage-gated potassium channels