Deletion of aquaporin-4 increases extracellular K(+) concentration during synaptic stimulation in mouse hippocampus

The coupling between the water channel aquaporin-4 (AQP4) and K(+) transport has attracted much interest. In this study, we assessed the effect of Aqp4 deletion on activity-induced [K(+)](o) changes in acute slices from hippocampus and corpus callosum of adult mice. We show that Aqp4 deletion has a layer-specific effect on [K(+)](o) that precisely mirrors the known effect on extracellular volume dynamics. In CA1, the peak [K(+)](o) in stratum radiatum during 20 Hz stimulation of Schaffer collateral/commissural fibers was significantly higher in Aqp4 (−/−) mice than in wild types, whereas no differences were observed throughout the [K(+)](o) recovery phase. In stratum pyramidale and corpus callosum, neither peak [K(+)](o) nor post-stimulus [K(+)](o) recovery was affected by Aqp4 deletion. Our data suggest that AQP4 modulates [K(+)](o) during synaptic stimulation through its effect on extracellular space volume.