title: Functional specialization and topographic segregation of hippocampal astrocytes.
abstract: Astrocytes have been suggested to play several roles in the complex control of brain microenvironment. However, they have been generally considered to constitute a homogeneous population of cells. Here we show that at least three electrophysiologically distinct types of astrocytes can be found in the mature hippocampus. These subpopulations of glia were characterized by expression of different ion currents. In astrocytes exposed to elevated K+, Cs+ prevented influx of K+ only in cells with inwardly rectifying currents (IIR). The topographic distribution of glia with Cs+-sensitive inward rectifying currents (involved in K+ buffering) was nonuniform. Cs+-sensitive astrocytes were predominantly found in CA3 radiatum, whereas most CA1 astrocytes were Cs+-insensitive. Functional significance of the spatial segregation of glial cells with inward rectification was addressed in slices that were bathed in Cs+-containing media. Under these conditions, neuronal stimulation induced spontaneous epileptiform activity, which first appeared in CA3 and was then synaptically propagated to CA1. Intracellular labeling of astrocytes with biocytin revealed that CA1 astrocytes are characterized by a high degree of cell-to-cell coupling; in contrast, cell labeling in CA3 revealed smaller groups and occasionally individual cells. Three individual biocytin-labeled cells had electrophysiological properties indistinguishable from Cs+-sensitive astrocytes but had morphology typical of oligodendroglia. These results provide evidence for a role of K+ uptake via IIR into astrocytes. The segregated expression of potassium channels in a subpopulation of astrocytes suggests that functionally specialized cell types are involved in K+ homeostasis.
authors.affiliation: Department of Neurological Surgery, University of Washington, Harborview Medical Center, Seattle, Washington 98104, USA.
authors.forename: R
authors.initials: R
authors.lastname: D'Ambrosio
authors.forename: J
authors.initials: J
authors.lastname: Wenzel
authors.forename: P A
authors.initials: PA
authors.lastname: Schwartzkroin
authors.forename: G M
authors.initials: GM
authors.lastname: McKhann
authors.forename: D
authors.initials: D
authors.lastname: Janigro
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D002586:Cesium / Q000494:pharmacology; D004553:Electric Conductivity; D017097:Electric Impedance; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology* / Q000503:physiopathology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000502:physiology; D007477:Ions; D008564:Membrane Potentials / Q000502:physiology; D009457:Neuroglia / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007473:Ion Channels; D007477:Ions; D002586:Cesium; D011188:Potassium