title: Aquaporin-4 regulates extracellular space volume dynamics during high-frequency synaptic stimulation: a gene deletion study in mouse hippocampus.
abstract: Little is known about the physiological roles of aquaporin-4 (AQP4) in the central nervous system. AQP4 water channels are concentrated in endfeet membranes of astrocytes but also localize to the fine astrocytic processes that abut central synapses. Based on its pattern of expression, we predicted that AQP4 could be involved in controlling water fluxes and changes in extracellular space (ECS) volume that are associated with activation of excitatory pathways. Here, we show that deletion of Aqp4 accentuated the shrinkage of the ECS that occurred in the mouse hippocampal CA1 region during activation of Schaffer collateral/commissural fibers. This effect was found in the stratum radiatum (where perisynaptic astrocytic processes abound) but not in the pyramidal cell layer (where astrocytic processes constitute but a minor volume fraction). For both genotypes the ECS shrinkage was most pronounced in the pyramidal cell layer. Our data attribute a physiological role to AQP4 and indicate that this water channel regulates extracellular volume dynamics in the mammalian brain.
authors.affiliation: Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Oslo, Norway.
authors.forename: Nadia Nabil
authors.initials: NN
authors.lastname: Haj-Yasein
authors.forename: Vidar
authors.initials: V
authors.lastname: Jensen
authors.forename: Ivar
authors.initials: I
authors.lastname: Østby
authors.forename: Stig W
authors.initials: SW
authors.lastname: Omholt
authors.forename: Juha
authors.initials: J
authors.lastname: Voipio
authors.forename: Kai
authors.initials: K
authors.lastname: Kaila
authors.forename: Ole P
authors.initials: OP
authors.lastname: Ottersen
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Hvalby
authors.forename: Erlend A
authors.initials: EA
authors.lastname: Nagelhus
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000172:deficiency*; D001253:Astrocytes / Q000502:physiology* / Q000648:ultrastructure; D055592:Biophysical Phenomena; D056547:CA1 Region, Hippocampal / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics*; D005110:Extracellular Space / Q000235:genetics*; D005731:Ganglionic Stimulants / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D018408:Patch-Clamp Techniques; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D017966:Pyramidal Cells / Q000502:physiology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D013569:Synapses / Q000235:genetics / Q000648:ultrastructure
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D005731:Ganglionic Stimulants; D005904:Glial Fibrillary Acidic Protein; D000644:Quaternary Ammonium Compounds; D010751:Phosphopyruvate Hydratase; C027917:tetramethylammonium