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A potassium channel-linked mechanism of glial cell swelling in the postischemic retina.

Abstract
The cellular mechanisms underlying glial cell swelling, a central cause of edema formation in the brain and retina, are not yet known. Here, we show that glial cells in the postischemic rat retina, but not in control retina, swell upon hypotonic stress. Swelling of control cells could be evoked when their K(+) channels were blocked. After transient ischemia, glial cells strongly downregulated their K(+) conductance and their prominent Kir4.1 protein expression at blood vessels and the vitreous body. In contrast, the expression of the aquaporin-4 (AQP4) (water channel) protein was only slightly altered after ischemia. Activation of D(2) dopaminergic receptors prevents the hypotonic glial cell swelling. The present results elucidate the coupling of transmembraneous water fluxes to K(+) currents in glial cells and reveal the role of altered K(+) channel expression in the development of cytotoxic edema. We propose a mechanism of postischemic glial cell swelling where a downregulation of their K(+) conductance prevents the emission of intracellularly accumulated K(+) ions, resulting in osmotically driven water fluxes from the blood into the glial cells via aquaporins. Inhibition of these water fluxes may be beneficial to prevent ischemia-evoked glial cell swelling.
AuthorsThomas Pannicke, Ianors Iandiev, Ortrud Uckermann, Bernd Biedermann, Franziska Kutzera, Peter Wiedemann, Hartwig Wolburg, Andreas Reichenbach, Andreas Bringmann
JournalMolecular and cellular neurosciences (Mol Cell Neurosci) Vol. 26 Issue 4 Pg. 493-502 (Aug 2004) ISSN: 1044-7431 [Print] United States
PMID15276152 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Aqp4 protein, rat
  • Aquaporin 4
  • Aquaporins
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Dopamine D2
  • Potassium
Topics
  • Animals
  • Aquaporin 4
  • Aquaporins (drug effects, metabolism)
  • Cell Membrane (drug effects, metabolism)
  • Cell Membrane Permeability (drug effects, physiology)
  • Cell Size (drug effects, physiology)
  • Disease Models, Animal
  • Down-Regulation (drug effects, physiology)
  • Edema (metabolism, pathology, physiopathology)
  • Ischemia (metabolism, pathology, physiopathology)
  • Membrane Potentials (drug effects, physiology)
  • Neuroglia (drug effects, metabolism, pathology)
  • Osmotic Pressure (drug effects)
  • Potassium (metabolism)
  • Potassium Channel Blockers (pharmacology)
  • Potassium Channels (drug effects, metabolism)
  • Potassium Channels, Inwardly Rectifying (drug effects, metabolism)
  • Rats
  • Rats, Long-Evans
  • Receptors, Dopamine D2 (agonists)
  • Retinal Diseases (metabolism, pathology, physiopathology)
  • Water-Electrolyte Balance (drug effects, physiology)

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