title: Potassium dependent regulation of astrocyte water permeability is mediated by cAMP signaling.
abstract: Astrocytes express potassium and water channels to support dynamic regulation of potassium homeostasis. Potassium kinetics can be modulated by aquaporin-4 (AQP4), the essential water channel for astrocyte water permeability regulation. We investigated whether extracellular potassium ([K(+)](o)) can regulate astrocyte water permeability and the mechanisms of such an effect. Studies were performed on rat primary astrocytes and a rat astrocyte cell line transfected with AQP4. We found that 10 mM [K(+)](o) caused an immediate, more than 40%, increase in astrocyte water permeability which was sustained in 5 min. The water channel AQP4 was a target for this regulation. Potassium induced a significant increase in intracellular cAMP as measured with a FRET based method and with enzyme immunoassay. We found that protein kinase A (PKA) could phosphorylate AQP4 in vitro. Further elevation of [K(+)](o) to 35 mM induced a global intracellular calcium response and a transient water permeability increase that was abolished in 5 min. When inwardly rectifying potassium (Kir)-channels were blocked, 10 mM [K(+)](o) also induced a calcium increase and the water permeability increase no longer persisted. In conclusion, we find that elevation of extracellular potassium regulates AQP4 and astrocyte water permeability via intracellular signaling involving cAMP. A prolonged increase of astrocyte water permeability is Kir-channel dependent and this response can be impeded by intracellular calcium signaling. Our results support the concept of coupling between AQP4 and potassium handling in astrocytes.
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet, Astrid Lindgren Children's Hospital, Stockholm, Sweden.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Song
authors.forename: Eli
authors.initials: E
authors.lastname: Gunnarson
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D006706:Homeostasis; D051379:Mice; D010539:Permeability; D010766:Phosphorylation; D011188:Potassium / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D061251:Primary Cell Culture; D051381:Rats; D015398:Signal Transduction; D014162:Transfection; D014867:Water / Q000378:metabolism*
chemical_list: C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D024661:Potassium Channels, Inwardly Rectifying; D014867:Water; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011188:Potassium; D002118:Calcium