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

Mol Cell Neurosci. 2004 Aug;26(4):493-502. doi: 10.1016/j.mcn.2004.04.005.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aquaporin 4
  • Aquaporins / drug effects
  • Aquaporins / metabolism
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cell Membrane Permeability / drug effects
  • Cell Membrane Permeability / physiology*
  • Cell Size / drug effects
  • Cell Size / physiology
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Edema / metabolism*
  • Edema / pathology
  • Edema / physiopathology
  • Ischemia / metabolism*
  • Ischemia / pathology
  • Ischemia / physiopathology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neuroglia / drug effects
  • Neuroglia / metabolism*
  • Neuroglia / pathology
  • Osmotic Pressure / drug effects
  • Potassium / metabolism
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism*
  • Potassium Channels, Inwardly Rectifying / drug effects
  • Potassium Channels, Inwardly Rectifying / metabolism
  • Rats
  • Rats, Long-Evans
  • Receptors, Dopamine D2 / agonists
  • Retinal Diseases / metabolism*
  • Retinal Diseases / pathology
  • Retinal Diseases / physiopathology
  • Water-Electrolyte Balance / drug effects
  • Water-Electrolyte Balance / physiology

Substances

  • Aqp4 protein, rat
  • Aquaporin 4
  • Aquaporins
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Dopamine D2
  • Potassium