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Critical role of aquaporin-4 (AQP4) in astrocytic Ca2+ signaling events elicited by cerebral edema.

Aquaporin-4 (AQP4) is a primary influx route for water during brain edema formation. Here, we provide evidence that brain swelling triggers Ca(2+) signaling in astrocytes and that deletion of the Aqp4 gene markedly interferes with these events. Using in vivo two-photon imaging, we show that hypoosmotic stress (20% reduction in osmolarity) initiates astrocytic Ca(2+) spikes and that deletion of Aqp4 reduces these signals. The Ca(2+) signals are partly dependent on activation of P2 purinergic receptors, which was judged from the effects of appropriate antagonists applied to cortical slices. Supporting the involvement of purinergic signaling, osmotic stress was found to induce ATP release from cultured astrocytes in an AQP4-dependent manner. Our results suggest that AQP4 not only serves as an influx route for water but also is critical for initiating downstream signaling events that may affect and potentially exacerbate the pathological outcome in clinical conditions associated with brain edema.

Pubmed ID: 21187412


  • Thrane AS
  • Rappold PM
  • Fujita T
  • Torres A
  • Bekar LK
  • Takano T
  • Peng W
  • Wang F
  • Rangroo Thrane V
  • Enger R
  • Haj-Yasein NN
  • Skare Ø
  • Holen T
  • Klungland A
  • Ottersen OP
  • Nedergaard M
  • Nagelhus EA


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

January 11, 2011

Associated Grants

  • Agency: NINDS NIH HHS, Id: P01 NS050315
  • Agency: NINDS NIH HHS, Id: P01NS050315
  • Agency: NINDS NIH HHS, Id: R01 NS075177
  • Agency: NINDS NIH HHS, Id: R01 NS078167
  • Agency: NINDS NIH HHS, Id: R01 NS078304
  • Agency: NINDS NIH HHS, Id: R01NS056188
  • Agency: NCRR NIH HHS, Id: TL1 RR024135

Mesh Terms

  • Adenosine Triphosphate
  • Animals
  • Aquaporin 4
  • Astrocytes
  • Brain
  • Brain Edema
  • Calcium
  • Edema
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osmosis
  • Photons
  • Signal Transduction
  • Water