The electrogenic Na⁺/HCO₃⁻ cotransporter (NBCe1) in astrocytes is crucial in regulation of acid–base homeostasis in the brain. Since many pathophysiological conditions in the brain have been associated with pH shifts we exposed primary mouse cortical and hippocampal astrocytes to prolonged low or high extracellular pH (pH_o) at constant extracellular bicarbonate concentration and investigated activation of astrocytes and regulation of NBCe1 by immunoblotting, biotinylation of surface proteins, and intracellular H⁺ recordings. High pH_o at constant extracellular bicarbonate caused upregulation of NBCe1 protein, surface expression and activity via upregulation of the astrocytic activation markers signal transducer and activator of transcription 3 (STAT3) signaling and glial fibrillary acidic protein expression. High pH_o‐induced increased NBCe1 protein expression was prevented in astrocytes from Stat3^flox/flox::Gfap^Cre/+ mice. In vitro, basal and high pH_o‐induced increased NBCe1 functional expression was impaired following inhibition of STAT3 phosphorylation. These results provide a novel regulation mode of NBCe1 protein and activity, highlight the importance of astrocyte reactivity on regulation of NBCe1 and implicate roles for NBCe1 in altering/modulating extracellular pH during development as well as of the microenvironment at sites of brain injuries and other pathophysiological conditions.

中文翻译：

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皮质星形胶质细胞中生电 Na+/HCO3-协同转运蛋白 1 (NBCe1) 功能表达的 STAT3 依赖性调节。

星形胶质细胞中的生电 Na ⁺ /HCO ₃ ^-协同转运蛋白（NBCe1）对于调节大脑中的酸碱平衡至关重要。由于大脑中的许多病理生理状况与 pH 值变化有关，我们将原代小鼠皮质和海马星形胶质细胞暴露于长时间的低或高细胞外 pH (pH _o )，细胞外碳酸氢盐浓度恒定，并通过免疫印迹、生物素化研究星形胶质细胞的活化和 NBCe1 的调节表面蛋白和细胞内 H ⁺记录。高pH _Ø在恒定的细胞外碳酸氢盐通过上调星形胶质细胞激活标记信号转导和转录激活因子 3 (STAT3) 信号和胶质纤维酸性蛋白表达导致 NBCe1 蛋白、表面表达和活性的上调。在来自Stat3 ^flox/flox ::Gfap ^{Cre/ +}小鼠的星形胶质细胞中，高 pH 值_o诱导的 NBCe1 蛋白表达增加被阻止。体外, 基础和高 pH 值_o抑制 STAT3 磷酸化后，诱导增加的 NBCe1 功能表达受损。这些结果提供了 NBCe1 蛋白和活性的新调节模式，突出了星形胶质细胞反应性对 NBCe1 调节的重要性，并暗示了 NBCe1 在发育过程中改变/调节细胞外 pH 值以及脑损伤和其他病理生理学部位的微环境中的作用。状况。