title: Inwardly Rectifying K+Currents in Cultured Oligodendrocytes from Rat Optic Nerve are Insensitive to pH.
abstract: Inwardly rectifying K+(Kir) channel expression signals at an advanced stage of maturation during oligodendroglial differentiation. Knocking down their expression halts the generation of myelin and produces severe abnormalities in the central nervous system. Kir4.1 is the main subunit involved in the tetrameric structure of Kir channels in glial cells; however, the precise composition of Kir channels expressed in oligodendrocytes (OLs) remains partially unknown, as participation of other subunits has been proposed. Kir channels are sensitive to H+; thus, intracellular acidification produces Kir current inhibition. Since Kir subunits have differential sensitivity to H+, we studied the effect of intracellular acidification on Kir currents expressed in cultured OLs derived from optic nerves of 12-day-old rats. Unexpectedly, Kir currents in OLs (2-4 DIV) did not change within the pH range of 8.0-5.0, as observed when using standard whole-cell voltage-clamp recording or when preserving cytoplasmic components with the perforated patch-clamp technique. In contrast, low pH inhibited astrocyte Kir currents, which was consistent with the involvement of the Kir4.1 subunit. The H+-insensitivity expressed in OL Kir channels was not intrinsic because Kir cloning showed no difference in the sequence reported for the Kir4.1, Kir2.1, or Kir5.1 subunits. Moreover, when Kir channels were heterologously expressed in Xenopus oocytes they behaved as expected in their general properties and sensitivity to H+. It is therefore concluded that Kir channel H+-sensitivity in OLs is modulated through an extrinsic mechanism, probably by association with a modulatory component or by posttranslational modifications.
authors.affiliation: Achucarro Basque Center for Neuroscience, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, Departamento de Neurociencias, Universidad del País Vasco, 48940, Leioa, Vizcaya, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pérez-Samartín
authors.affiliation: Laboratorio de Neurofisiología Celular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla 3001, Juriquilla, 76230, Querétaro, Mexico.
authors.forename: Edith
authors.initials: E
authors.lastname: Garay
authors.affiliation: Laboratorio de Neurofisiología Celular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla 3001, Juriquilla, 76230, Querétaro, Mexico.
authors.forename: Juan Pablo H
authors.initials: JPH
authors.lastname: Moctezuma
authors.affiliation: Laboratorio de Neurofisiología Celular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla 3001, Juriquilla, 76230, Querétaro, Mexico.
authors.forename: Abraham
authors.initials: A
authors.lastname: Cisneros-Mejorado
authors.affiliation: Achucarro Basque Center for Neuroscience, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, Departamento de Neurociencias, Universidad del País Vasco, 48940, Leioa, Vizcaya, Spain.
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Sánchez-Gómez
authors.affiliation: Laboratorio de Neurofisiología Celular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla 3001, Juriquilla, 76230, Querétaro, Mexico.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Martel-Gallegos
authors.affiliation: Laboratorio de Neurofisiología Celular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla 3001, Juriquilla, 76230, Querétaro, Mexico.
authors.forename: Leticia
authors.initials: L
authors.lastname: Robles-Martínez
authors.affiliation: Achucarro Basque Center for Neuroscience, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, Departamento de Neurociencias, Universidad del País Vasco, 48940, Leioa, Vizcaya, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Canedo-Antelo
authors.affiliation: Achucarro Basque Center for Neuroscience, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, Departamento de Neurociencias, Universidad del País Vasco, 48940, Leioa, Vizcaya, Spain. carlos.matute@ehu.eus.
authors.forename: Carlos
authors.initials: C
authors.lastname: Matute
authors.affiliation: Laboratorio de Neurofisiología Celular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla 3001, Juriquilla, 76230, Querétaro, Mexico. arellano.ostoa@comunidad.unam.mx.
authors.forename: Rogelio O
authors.identifier: http://orcid.org/0000-0002-8646-250X
authors.initials: RO
authors.lastname: Arellano
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials / Q000502:physiology; D009836:Oligodendroglia / Q000502:physiology*; D009900:Optic Nerve / Q000166:cytology / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014982:Xenopus laevis
chemical_list: D024661:Potassium Channels, Inwardly Rectifying
keywords: Inwardly rectifying K+ channel; Kir4.1; Oligodendrocyte; pH sensitivity