Dystrophin Dp71 is Critical for the Clustered Localization of Potassium Channels in Retinal Glial Cells

Nathan C. Connors, Paulo Kofuji

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94 Scopus citations

Abstract

The Müller cell is the principal glial cell of the vertebrate retina. The primary conductance in Müller cells is the inwardly rectifying potassium channel Kir4.1 (BIR10 and KAB-2), which is highly concentrated at the endfeet at the vitreal border and to processes enveloping blood vessels. Such asymmetric and clustered distribution of Kir4.1 channels in Müller cells is thought to be critical for the buffering of extracellular potassium concentration in retina. Herein we investigated whether the distribution and functional properties of Kir4.1 channels are dependent on expression of the Dp71, a dystrophin isoform expressed in Müller cells. Kir4.1 distribution was determined in mouse retinal sections and whole mounts using anti-Kir4.1 antibodies and confocal microscopy. In Müller cells from wild-type mice, Kir4.1 is highly clustered in their endfeet and perivascular processes. In contrast, in Müller cells from the mdx3Cv mouse, which lacks the expression of Dp71, the Kir4.1 immunoreactivity is evenly distributed throughout the cell membrane. Surface expression of Kir4.1 is not affected in mdx3Cv Müller cells as current density of barium-sensitive inward currents in mdx3Cv Müller cells are not different from wild type. Focal extracellular potassium increases in isolated Müller cells shows that Kir channels in the mdx3Cv cells, as opposed to wild type, are less prominently concentrated in their endfeet. In summary, our data indicate that Dp71 is critical for the clustering but not membrane expression of Kir4.1 in mouse Müller cells. These results point to a new role for dystrophin in glial cells.

Original languageEnglish (US)
Pages (from-to)4321-4327
Number of pages7
JournalJournal of Neuroscience
Volume22
Issue number11
DOIs
StatePublished - Jun 1 2002

Keywords

  • Immunolocalization
  • Inward-rectifying potassium channel
  • Kir4.1
  • Müller cells
  • Potassium siphoning
  • Retina

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