The impact of astrocytic gap junctional coupling on potassium buffering in the hippocampus

J Neurosci. 2006 May 17;26(20):5438-47. doi: 10.1523/JNEUROSCI.0037-06.2006.

Abstract

Astrocytic gap junctions have been suggested to contribute to spatial buffering of potassium in the brain. Direct evidence has been difficult to gather because of the lack of astrocyte-specific gap junction blockers. We obtained mice with coupling-deficient astrocytes by crossing conditional connexin43-deficient mice with connexin30(-/-) mice. Similar to wild-type astrocytes, genetically uncoupled hippocampal astrocytes displayed negative resting membrane potentials, time- and voltage-independent whole-cell currents, and typical astrocyte morphologies. Astrocyte densities were also unchanged. Using potassium-selective microelectrodes, we assessed changes in potassium buffering in hippocampal slices of mice with coupling-deficient astrocytes. We demonstrate that astrocytic gap junctions accelerate potassium clearance, limit potassium accumulation during synchronized neuronal firing, and aid in radial potassium relocation in the stratum lacunosum moleculare. Furthermore, slices of mice with coupling-deficient astrocytes displayed a reduced threshold for the generation of epileptiform events. However, it was evident that radial relocation of potassium in the stratum radiatum was not dependent on gap junctional coupling. We suggest that the perpendicular array of individual astrocytes in the stratum radiatum makes these cells ideally suited for spatial buffering of potassium released by pyramidal cells, independent of gap junctions. In general, a surprisingly large capacity for K+ clearance was conserved in mice with coupling-deficient astrocytes, indicating that gap junction-dependent processes only partially account for K+ buffering in the hippocampus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Buffers
  • Cell Communication / genetics*
  • Cell Shape / drug effects
  • Cell Shape / physiology
  • Connexin 30
  • Connexin 43 / genetics
  • Connexins / genetics
  • Electric Stimulation
  • Gap Junctions / drug effects
  • Gap Junctions / genetics
  • Gap Junctions / metabolism*
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Membrane Potentials / drug effects
  • Membrane Potentials / genetics
  • Mice
  • Mice, Knockout
  • Organ Culture Techniques
  • Potassium / metabolism*
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism
  • Pyramidal Cells / metabolism

Substances

  • Buffers
  • Connexin 30
  • Connexin 43
  • Connexins
  • Gjb6 protein, mouse
  • Potassium Channels
  • Potassium