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

Proceedings of the National Academy of Sciences - PNAS, 2011-01, Vol.108 (2), p.846-851 [Peer Reviewed Journal]

ISSN: 0027-8424 ;EISSN: 1091-6490 ;DOI: 10.1073/pnas.1015217108 ;PMID: 21187412

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Title:
Critical role of aquaporin-4 (AQP4) in astrocytic Ca²⁺ signaling events elicited by cerebral edema
Author: Thrane, Alexander S ; Rappold, Phillip M ; Fujita, Takumi ; Torres, Arnulfo ; Bekar, Lane K ; Takano, Takahiro ; Peng, Weiguo ; Wang, Fushun ; Thrane, Vinita Rangroo ; Enger, Rune ; Haj-Yasein, Nadia N ; Skare, Øivind ; Holen, Torgeir ; Klungland, Arne ; Ottersen, Ole P ; Nedergaard, Maiken ; Nagelhus, Erlend A
Subjects: Adenosine Triphosphate - chemistry ; Animals ; Aquaporin 4 - chemistry ; Aquaporin 4 - genetics ; Astrocytes ; Astrocytes - metabolism ; Biological Sciences ; Brain - pathology ; Brain edema ; Brain Edema - metabolism ; Calcium - metabolism ; Edema - pathology ; Female ; Genotypes ; Imaging ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neuroglia ; Neurons ; Neuroscience ; Osmosis ; Photons ; Signal Transduction ; Swelling ; Water - chemistry ; Water injection
Is Part Of: Proceedings of the National Academy of Sciences - PNAS, 2011-01, Vol.108 (2), p.846-851
Description: Aquaporin-4 (AQP4) is a primary influx route for water during brain edema formation. Here, we provide evidence that brain swelling triggers Ca²⁺ 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 Ca²⁺ spikes and that deletion of Aqp4 reduces these signals. The Ca²⁺ 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.
Publisher: United States: National Academy of Sciences
Language: English
Identifier: ISSN: 0027-8424
EISSN: 1091-6490
DOI: 10.1073/pnas.1015217108
PMID: 21187412
Source: GFMER Free Medical Journals
MEDLINE
PubMed Central

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

ISSN: 0027-8424 ;EISSN: 1091-6490 ;DOI: 10.1073/pnas.1015217108 ;PMID: 21187412

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