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Anoctamin-1 is a calcium-dependent chloride channel (CaCC) in Müller cells involved in cell volume regulation.
Glia 74:e70170 (2026)
Previous functional data showed the presence of Cl- channels in Müller cells, among them Ca2+-dependent Cl- channels (CaCC). An important step to understanding the role of CaCC in Müller cell function is the clarification of their molecular identity. Here, we found protein expression of the CaCC anoctamin-1 (Ano1, formerly TMEM16A) in Müller cells in retinal sagittal sections of mouse and rat using immunohistochemistry and proteomic analysis, as well as in the Müller cell lines ImM10 (murine) and MIO-M1 (human), accompanied by Western blot. Patch-clamp analysis of both cell lines under K+-free conditions showed the activation of membrane currents through an increase in intracellular free Ca2+ using either ionomycin, ATP, or adenosine. These currents were sensitive to several blockers: the broad anoctamin blocker niflumic acid, the CaCC blocker CaCCinh-A01, and the Ano1 blocker T16Ainh-A01. To further explore the function of Ano1 in Müller cells, we investigated the adenosine-dependent volume regulation in mouse Müller cells in freshly isolated sagittal sections under hypoosmotic challenge by blockage of K+ channels. T16Ainh-A01 partially reversed the beneficial effect of adenosine on Müller cell volume regulation. We conclude that Ano1 is one of the first functionally validated Cl- channels in Müller cells. Ano1 seems to contribute to the adenosine-driven regulation of ion flow across the Müller cell membrane, which is crucial for clearing extracellular fluid from the retina.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Ano1 ; Cacc ; Cl− Channels ; Müller Cells ; Tmem16a ; Anoctamin‐1 ; Volume Regulation
ISSN (print) / ISBN
0894-1491
e-ISSN
1098-1136
Journal
Glia
Quellenangaben
Volume: 74,
Issue: 8,
Article Number: e70170
Publisher
Wiley
Reviewing status
Peer reviewed
Institute(s)
CF Metabolomics & Proteomics (CF-MPC)
Grants
DOG-Deutsche Ophthalmologische Gesellschaft
Charite - Universitatsmedizin Berlin
Charite - Universitatsmedizin Berlin