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Inwardly Rectifying K+ Currents in Cultured Oligodendrocytes from Rat Optic Nerve are Insensitive to pH

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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.

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Acknowledgements

We thank Saioa Marcos, Horacio Leyva, and Leonor Casanova for technical assistance, and Jessica González Norris for editing the manuscript. This work is supported by the Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica DGAPA-UNAM [Grant IN205615] and Consejo Nacional de Ciencia y Tecnología, México [Grant 252121] to R.O.A.; and Ministerio de Economía y Competitividad/Fondos Europeos de Desarrollo Regional [Grants SAF2016-75292-R and SAF2013-45084-R] and the Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas [Grant PRY-15-404] to C.M.

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    Authors and Affiliations

    1. 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

      Alberto Pérez-Samartín, María Victoria Sánchez-Gómez, Manuel Canedo-Antelo & Carlos Matute

    2. Laboratorio de Neurofisiología Celular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla 3001, Juriquilla, 76230, Querétaro, Mexico

      Edith Garay, Juan Pablo H. Moctezuma, Abraham Cisneros-Mejorado, Guadalupe Martel-Gallegos, Leticia Robles-Martínez & Rogelio O. Arellano

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    1. Alberto Pérez-Samartín
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    Correspondence to Carlos Matute or Rogelio O. Arellano.

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    Alberto Pérez-Samartín and Edith Garay have contributed equally to this work.

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    Pérez-Samartín, A., Garay, E., Moctezuma, J.P.H. et al. Inwardly Rectifying K+ Currents in Cultured Oligodendrocytes from Rat Optic Nerve are Insensitive to pH. Neurochem Res 42, 2443–2455 (2017). https://doi.org/10.1007/s11064-017-2242-8

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