Glial K+ clearance and cell swelling: Key roles for cotransporters and pumps

摘要

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.