The electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), is the major bicarbonate transporter expressed in astrocytes. It is highly sensitive for bicarbonate, and the main regulator of intracellular-, extracellular-, and synaptic pH, thereby modulating neuronal excitability. However, despite these essential functions, the molecular mechanisms underlying NBCe1-mediated astrocytic response to extracellular pH changes are mostly unknown. Using primary cortical astrocyte cultures we have investigated the effect of long-term extracellular metabolic alkalosis on regulation of NBCe1 using functional assays and phosphoproteomic analysis.