| First Author | Liu Y | Year | 2025 |
| Journal | Glia | Volume | 73 |
| Issue | 12 | Pages | 2353-2368 |
| PubMed ID | 40719051 | Mgi Jnum | J:372976 |
| Mgi Id | MGI:8250688 | Doi | 10.1002/glia.70073 |
| Citation | Liu Y, et al. (2025) Acid-Sensing PAC Channel Promotes Astrocyte Acidosis in Ischemic Stroke. Glia |
| abstractText | Astrocyte is critically involved in the central nervous system homeostasis and initiates tissue pathology in response to insults to the central nervous system. However, whether and how astrocytes sense micro-environmental changes, such as ischemic stroke-associated acidification, remains largely unknown. Here we show that the proton-activated chloride (PAC) channel is widely expressed in glial cells in the brain and functionally mediates acid-induced chloride influx. Moreover, conditional knockout of the PAC channel in astrocytes, but not in microglia, reduced infarct volume in a mouse model of ischemic stroke induced by middle cerebral artery occlusion/reperfusion (MCAO/R). Rather than the classic role of chloride channels in cell volume dysregulation-related cell death, activation of the PAC channel contributes to cell apoptosis via the Akt/Bax/Caspase 3 pathway in astrocytes and promotes inflammatory mediator release from astrocytes in response to pH oscillation and oxidative stress. Collectively, our results uncover a role of the PAC channel in astrocyte acidosis, providing a potential therapeutic target for neuroprotection in ischemic stroke. |
