Impact of aquaporin-4 channels on K+ buffering and gap junction coupling in the hippocampus

Glia. 2011 Jun;59(6):973-80. doi: 10.1002/glia.21169. Epub 2011 Mar 28.

Abstract

Aquaporin-4 (AQP4) is the main water channel in the brain and primarily localized to astrocytes where the channels are thought to contribute to water and K(+) homeostasis. The close apposition of AQP4 and inward rectifier K(+) channels (Kir4.1) led to the hypothesis of direct functional interactions between both channels. We investigated the impact of AQP4 on stimulus-induced alterations of the extracellular K(+) concentration ([K(+)](o)) in murine hippocampal slices. Recordings with K(+)-selective microelectrodes combined with field potential analyses were compared in wild type (wt) and AQP4 knockout (AQP4(-/-)) mice. Astrocyte gap junction coupling was assessed with tracer filling during patch clamp recording. Antidromic fiber stimulation in the alveus evoked smaller increases and slower recovery of [K(+)](o) in the stratum pyramidale of AQP4(-/-) mice indicating reduced glial swelling and a larger extracellular space when compared with control tissue. Moreover, the data hint at an impairment of the glial Na(+)/K(+) ATPase in AQP4-deficient astrocytes. In a next step, we investigated the laminar profile of [K(+)](o) by moving the recording electrode from the stratum pyramidale toward the hippocampal fissure. At distances beyond 300 μm from the pyramidal layer, the stimulation-induced, normalized increases of [K(+)](o) in AQP4(-/-) mice exceeded the corresponding values of wt mice, indicating facilitated spatial buffering. Astrocytes in AQP4(-/-) mice also displayed enhanced tracer coupling, which might underlie the improved spatial re- distribution of [K(+)](o) in the hippocampus. These findings highlight the role of AQP4 channels in the regulation of K(+) homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aquaporin 4 / deficiency
  • Aquaporin 4 / physiology*
  • Buffers
  • Cell Communication / genetics
  • Gap Junctions / enzymology
  • Gap Junctions / genetics
  • Gap Junctions / metabolism*
  • Hippocampus / enzymology
  • Hippocampus / metabolism*
  • Homeostasis / genetics
  • Membrane Potentials / genetics
  • Mice
  • Mice, Knockout
  • Organ Culture Techniques
  • Patch-Clamp Techniques / methods
  • Potassium / metabolism*
  • Potassium / physiology
  • Potassium Channels, Inwardly Rectifying / physiology*
  • Sodium-Potassium-Exchanging ATPase / metabolism

Substances

  • Aqp4 protein, mouse
  • Aquaporin 4
  • Buffers
  • Kcnj10 (channel)
  • Potassium Channels, Inwardly Rectifying
  • Sodium-Potassium-Exchanging ATPase
  • Potassium