Relationship between glial potassium regulation and axon excitability: a role for glial Kir4.1 channels

Glia. 2012 Apr;60(4):651-60. doi: 10.1002/glia.22299. Epub 2012 Jan 30.


Uptake of K(+) released by axons during action potential propagation is a major function of astrocytes. Here, we demonstrate the importance of glial inward rectifying potassium channels (Kir) in regulating extracellular K(+) ([K(+)](o)) and axonal electrical activity in CNS white matter of the mouse optic nerve. Increasing optic nerve stimulation frequency from 1 Hz to 10-35 Hz for 120 s resulted in a rise in [K(+)](o) and consequent decay in the compound action potential (CAP), a measure of reduced axonal activity. On cessation of high frequency stimulation, rapid K(+) clearance resulted in a poststimulus [K(+)](o) undershoot, followed by a slow recovery of [K(+)](o) and the CAP, which were more protracted with increasing stimulation frequency. Blockade of Kir (100 μM BaCl(2)) slowed poststimulus recovery of [K(+)](o) and the CAP at all stimulation frequencies, indicating a primary function of glial Kir was redistributing K(+) to the extracellular space to offset active removal by Na(+)-K(+) pumps. At higher levels of axonal activity, Kir blockade also increased [K(+)](o) accumulation, exacerbating the decline in the CAP and impeding its subsequent recovery. In the Kir4.1-/- mouse, astrocytes displayed a marked reduction of inward currents and were severely depolarized, resulting in retarded [K(+)](o) regulation and reduced CAP. The results demonstrate the importance of glial Kir in K(+) spatial buffering and sustaining axonal activity in the optic nerve. Glial Kir have increasing importance in K(+) clearance at higher levels of axonal activity, helping to maintain the physiological [K(+)](o) ceiling and ensure the fidelity of signaling between the retina and brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Axons / drug effects
  • Axons / physiology*
  • Barium Compounds / pharmacology
  • Biophysical Phenomena / drug effects
  • Biophysical Phenomena / genetics
  • Biophysics
  • Chlorides / pharmacology
  • Electric Stimulation
  • Female
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neuroglia / drug effects
  • Neuroglia / physiology*
  • Optic Nerve / cytology
  • Optic Nerve / physiology*
  • Patch-Clamp Techniques
  • Potassium / metabolism*
  • Potassium Channels, Inwardly Rectifying / deficiency
  • Potassium Channels, Inwardly Rectifying / metabolism*
  • Tissue Culture Techniques


  • Barium Compounds
  • Chlorides
  • Kcnj10 (channel)
  • Potassium Channels, Inwardly Rectifying
  • barium chloride
  • Potassium