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

Nadia Nabil Haj-Yasein,Øivind Hvalby,Cecilie Elisabeth Bugge,Vidar Jensen,Ivar Østby,Erlend Arnulf Nagelhus,Ole Petter Ottersen

doi:10.1007/s00429-014-0767-z

Nadia Nabil Haj-Yasein, Øivind Hvalby + Show 5 more

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https://doi.org/10.1007/s00429-014-0767-z

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Abstract

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.

Highlights

Synaptic activity causes release of K? into the extracellular space
We show that Aqp4 deletion has a layer-specific effect on [K?]o that precisely mirrors the known effect on extracellular volume dynamics
Kir4.1 immunoreactivity in wild type animals resembled that of AQP4, but the signal was weaker around vessels (Fig. 1b, d)

Summary

Introduction

Synaptic activity causes release of K? into the extracellular space. The excess K? must be rapidly removed in order to avoid hyperexcitation and epileptic seizures. A number of membrane transporters and channels contribute to clearance of K? Foremost among these are the Na,K-ATPase, which is responsible for a major fraction of the energy expenditure in brain, and the Kir4.1 inwardly rectifying K? Clearance (Nielsen et al 1997). This hypothesis was strengthened by the finding that AQP4 was colocalized with Kir4.1 in endfeet of retinal Muller cells (Nagelhus et al 1999) and that selective removal of AQP4 from endfoot membranes delayed K? Clearance following highfrequency activation of hippocampal synapses (AmiryMoghaddam et al 2003). Clearance was observed following Aqp deletion, albeit only when [K?]o was mildly increased (Strohschein et al 2011) Delayed K? clearance was observed following Aqp deletion, albeit only when [K?]o was mildly increased (Strohschein et al 2011)

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