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.