title: Glial K⁺ clearance and cell swelling: key roles for cotransporters and pumps.
abstract: An important feature of neuronal signalling is the increased concentration of K(+) in the extracellular space. The K(+) concentration is restored to its original basal level primarily by uptake into nearby glial cells. The molecular mechanisms by which K(+) is transferred from the extracellular space into the glial cell are debated. Although spatial buffer currents may occur, their quantitative contribution to K(+) clearance is uncertain. The concept of spatial buffering of K(+) precludes intracellular K(+) accumulation and is therefore (i) difficult to reconcile with the K(+) accumulation repeatedly observed in glial cells during K(+) clearance and (ii) incompatible with K(+)-dependent glial cell swelling. K(+) uptake into non-voltage clamped cultured glial cells is carried out by the Na(+)/K(+)-ATPase and the Na(+)/K(+)/Cl(-) cotransporter in combination. In brain slices and intact optic nerve, however, only the Na(+)/K(+)-ATPase has been demonstrated to be involved in stimulus-evoked K(+) clearance. The glial cell swelling associated with K(+) clearance is prevented under conditions that block the activity of the Na(+)/K(+)/Cl(-) cotransporter. The Na(+)/K(+)/Cl(-) cotransporter is activated by increased K(+) concentration and cotransports water along with its substrates. It thereby serves as a K(+)-dependent molecular water pump under conditions of increased extracellular K(+) load.
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, Copenhagen, Denmark. macaulay@sund.ku.dk
authors.forename: Nanna
authors.initials: N
authors.lastname: Macaulay
authors.forename: Thomas
authors.initials: T
authors.lastname: Zeuthen
mesh_terms: D000818:Animals; D006706:Homeostasis; D006801:Humans; D026901:Membrane Transport Proteins / Q000502:physiology*; D009457:Neuroglia / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins; D011188:Potassium