title: Block of neural Kv1.1 potassium channels for neuroinflammatory disease therapy.
abstract: OBJECTIVE
  We asked whether blockade of voltage-gated K+ channel Kv1.1, whose altered axonal localization during myelin insult and remyelination may disturb nerve conduction, treats experimental autoimmune encephalomyelitis (EAE).
  
  
  METHODS
  Electrophysiological, cell proliferation, cytokine secretion, immunohistochemical, clinical, brain magnetic resonance imaging, and spectroscopy studies assessed the effects of a selective blocker of Kv1.1, BgK-F6A, on neurons and immune cells in vitro and on EAE-induced neurological deficits and brain lesions in Lewis rats.
  
  
  RESULTS
  BgK-F6A increased the frequency of miniature excitatory postsynaptic currents in neurons and did not affect T-cell activation. EAE was characterized by ventriculomegaly, decreased apparent diffusion coefficient, and decreased (phosphocreatine + beta-adenosine triphosphate)/inorganic phosphate ratio. Reduced apparent diffusion coefficient and impaired energy metabolism indicate astrocytic edema. Intracerebroventricularly BgK-F6A-treated rats showed attenuated clinical EAE with unexpectedly reduced ventriculomegaly and preserved apparent diffusion coefficient values and (phosphocreatine + beta-adenosine triphosphate)/inorganic phosphate ratio. Thus, under BgK-F6A treatment, brain damage was dramatically reduced and energy metabolism maintained.
  
  
  CONCLUSIONS
  Kv1.1 blockade may target neurons and astrocytes, and modulate neuronal activity and neural cell volume, which may partly account for the attenuation of the neurological deficits. We propose that Kv1.1 blockade has a broad therapeutic potential in neuroinflammatory diseases (multiple sclerosis, stroke, and trauma).
authors.affiliation: Service d'Immunologie, Faculté de Médecine, Université de la Méditerranée, Marseille, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Beraud
authors.affiliation: Centre de Résonance Magnétique Biologique et Médicale, Unité Mixte de Recherche Centre National de la Recherche Scientifique 6612, Faculté de Médecine, Université de la Méditerranée, Marseille, France.
authors.forename: Angèle
authors.initials: A
authors.lastname: Viola
authors.affiliation: Laboratoire d'Ingénierie des Protéines, Unité Mixte de Recherche Centre National de la Recherche Scientifique 6560; Institut Fédératif de Recherche Jean Roche, Marseille, France.
authors.forename: Imed
authors.initials: I
authors.lastname: Regaya
authors.affiliation: Centre de Résonance Magnétique Biologique et Médicale, Unité Mixte de Recherche Centre National de la Recherche Scientifique 6612, Faculté de Médecine, Université de la Méditerranée, Marseille, France.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Confort-Gouny
authors.affiliation: Laboratoire d'Otologie, Equipe Propre Institut National de la Sante et de la Recherche Médicale 19902, Institut Fédératif de Recherche Jean Roche, Marseille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Siaud
authors.affiliation: Centre de Résonance Magnétique Biologique et Médicale, Unité Mixte de Recherche Centre National de la Recherche Scientifique 6612, Faculté de Médecine, Université de la Méditerranée, Marseille, France.
authors.forename: Danielle
authors.initials: D
authors.lastname: Ibarrola
authors.affiliation: Centre de Résonance Magnétique Biologique et Médicale, Unité Mixte de Recherche Centre National de la Recherche Scientifique 6612, Faculté de Médecine, Université de la Méditerranée, Marseille, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Le Fur
authors.affiliation: Service d'Immunologie, Faculté de Médecine, Université de la Méditerranée, Marseille, France.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Barbaria
authors.affiliation: Laboratoire de Biopathologie Nerveuse et Musculaire, Faculté de Médecine, Université de la Méditerranée, Marseille, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Pellissier
authors.affiliation: Laboratoire d'Ingénierie des Protéines, Unité Mixte de Recherche Centre National de la Recherche Scientifique 6560; Institut Fédératif de Recherche Jean Roche, Marseille, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Sabatier
authors.affiliation: Institut de Neurobiologie de la Méditerranée, Institut National de la Santé et de la Recherche Médicale U29, Marseille, France.
authors.forename: Igor
authors.initials: I
authors.lastname: Medina
authors.affiliation: Centre de Résonance Magnétique Biologique et Médicale, Unité Mixte de Recherche Centre National de la Recherche Scientifique 6612, Faculté de Médecine, Université de la Méditerranée, Marseille, France.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Cozzone
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001812:Blood-Brain Barrier / Q000187:drug effects; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003064:Cnidarian Venoms / Q000494:pharmacology* / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051381:Rats; D011917:Rats, Inbred Lew; D051637:Shaker Superfamily of Potassium Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D003064:Cnidarian Venoms; D051637:Shaker Superfamily of Potassium Channels; C104455:toxin BgK