title: Relationship between glial potassium regulation and axon excitability: a role for glial Kir4.1 channels.
abstract: 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.
authors.affiliation: Institute of Biomedical and Biomolecular Science (IBBS), School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, United Kingdom.
authors.forename: Virginia
authors.initials: V
authors.lastname: Bay
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Butt
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D017609:Barium Compounds / Q000494:pharmacology; D055592:Biophysical Phenomena / Q000187:drug effects / Q000235:genetics; D001703:Biophysics; D002712:Chlorides / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D009900:Optic Nerve / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000172:deficiency / Q000378:metabolism*; D046509:Tissue Culture Techniques; D000098854:Kcnj10 Channel
chemical_list: D017609:Barium Compounds; D002712:Chlorides; D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; C024986:barium chloride; D011188:Potassium