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Aquaporin 4 (AQP4) is the predominant water channel in the mammalian brain and is mainly expressed in the perivascular glial endfeet at the brain-blood interface. Based on studies on AQP4 mice, AQP4 has been assigned physiological roles in stimulus-induced K clearance, paravascular fluid flow, and brain edema formation. Conflicting data have been presented on the role of AQP4 in K clearance and associated extracellular space shrinkage and on the stroke-induced alterations of AQP4 expression levels during edema formation, raising questions about the functional importance of AQP4 in these (patho)physiological aspects. Phosphorylation-dependent gating of AQP4 has been proposed as a regulatory mechanism for AQP4-mediated osmotic water transport. This paradigm was, however, recently challenged by experimental evidence and molecular dynamics simulations. Regulatory patterns and physiological roles for AQP4 thus remain to be fully explored. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]