4.6 Article

Tandem-pore domain potassium channels are functionally expressed in retinal (Muller) glial cells

期刊

GLIA
卷 53, 期 3, 页码 266-276

出版社

WILEY
DOI: 10.1002/glia.20280

关键词

TASK channels; membrane potential; spatial buffering; cell swelling

资金

  1. NCRR NIH HHS [G12RR03035] Funding Source: Medline
  2. NIGMS NIH HHS [SO6-GM50695] Funding Source: Medline
  3. NINDS NIH HHS [NS39408, S11-NS48201] Funding Source: Medline

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Tandem-pore domain (2P-domain) K+-channels regulate neuronal excitability, but their function in glia, particularly, in retinal glial cells, is unclear. We have previously demonstrated the immunocytochemical localization of the 2P-domain K+ channels TASK-1 and TASK-2 in retinal Muller glial cells of amphibians. The purpose of the present study was to determine whether these channels were functional, by employing whole-cell recording from frog and mammalian (guinea pig, rat and mouse) Muller cells and confocal microscopy to monitor swelling in rat Muller cells. TASK-like immunolabel was localized in these cells. The currents mediated by 2P-domain channels were studied in isolation after blocking Kir, K-A, K-D, and BK channels. The remaining cell conductance was mostly outward and was depressed by acid pH, bupivacaine, methanandamide, quinine, and clofilium, and activated by alkaline pH in a manner consistent with that described for TASK channels. Arachidonic acid (an activator of TREK channels) had no effect on this conductance. Blockade of the conductance with bupivacaine depolarized the Muller cell membrane potential by about 50%. In slices of the rat retina, adenosine inhibited osmotic glial cell swelling via activation of A1 receptors and subsequent opening of 2P-domain K+ channels. The swelling was strongly increased by clofilium and quinine (inhibitors of 2P-domain K+ channels). These data suggest that 2P-domain K+ channels are involved in homeostasis of glial cell volume, in activity-dependent spatial K+ buffering and may play a role in maintenance of a hyperpolarized membrane potential especially in conditions where Kir channels are blocked or downregulated. (C) 2005 Wiley-Liss, Inc.

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