title: Impact of aquaporin-4 channels on K+ buffering and gap junction coupling in the hippocampus.
abstract: Aquaporin-4 (AQP4) is the main water channel in the brain and primarily localized to astrocytes where the channels are thought to contribute to water and K(+) homeostasis. The close apposition of AQP4 and inward rectifier K(+) channels (Kir4.1) led to the hypothesis of direct functional interactions between both channels. We investigated the impact of AQP4 on stimulus-induced alterations of the extracellular K(+) concentration ([K(+)](o)) in murine hippocampal slices. Recordings with K(+)-selective microelectrodes combined with field potential analyses were compared in wild type (wt) and AQP4 knockout (AQP4(-/-)) mice. Astrocyte gap junction coupling was assessed with tracer filling during patch clamp recording. Antidromic fiber stimulation in the alveus evoked smaller increases and slower recovery of [K(+)](o) in the stratum pyramidale of AQP4(-/-) mice indicating reduced glial swelling and a larger extracellular space when compared with control tissue. Moreover, the data hint at an impairment of the glial Na(+)/K(+) ATPase in AQP4-deficient astrocytes. In a next step, we investigated the laminar profile of [K(+)](o) by moving the recording electrode from the stratum pyramidale toward the hippocampal fissure. At distances beyond 300 μm from the pyramidal layer, the stimulation-induced, normalized increases of [K(+)](o) in AQP4(-/-) mice exceeded the corresponding values of wt mice, indicating facilitated spatial buffering. Astrocytes in AQP4(-/-) mice also displayed enhanced tracer coupling, which might underlie the improved spatial re- distribution of [K(+)](o) in the hippocampus. These findings highlight the role of AQP4 channels in the regulation of K(+) homeostasis.
authors: Institute of Cellular Neurosciences, University of Bonn, Bonn, Germany. christian.steinhaeuser@ukb.uni-bonn.de
authors: Susan
authors: S
authors: Strohschein
authors: Kerstin
authors: K
authors: Hüttmann
authors: Siegrun
authors: S
authors: Gabriel
authors: Devin K
authors: DK
authors: Binder
authors: Uwe
authors: U
authors: Heinemann
authors: Christian
authors: C
authors: Steinhäuser
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000172:deficiency / Q000502:physiology*; D002021:Buffers; D002450:Cell Communication / Q000235:genetics; D017629:Gap Junctions / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques / Q000379:methods; D011188:Potassium / Q000378:metabolism* / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D000098854:Kcnj10 Channel
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D002021:Buffers; D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium