Regulation of Sodium/bicarbonate Co‐transporter 1, NBCe1, in Murine Hippocampal and Cortical Astrocytes

Abstract

The product of the Slc4a4 gene, the Na+/HCO3‐ cotransporter 1 (NBCe1), is a key pH regulating plasma membrane transporter and broadly expressed in several cell types. It is well established that depolarization‐induced alkalinization of glial cells is ascribed to uptake of bicarbonate via the electrogenic NBCe1, activated by the K+‐induced membrane <a>depolarization</a>. However, in contrast to epithelial cells the molecular pathways underlying NBCe1 transcriptional regulation and trafficking in neural cells are largely unknown. In the present study we examined regulation of astrocyte NBCe1 and elucidated the underlying signalling pathways. Expression, regulation, and activity of NBCe1 was examined in acute hippocampal slices and primary cultured hippocampal and cortical astrocytes using the 4AP (4‐aminopyridine) model and following extracellular pH changes in the presence or absence of inhibitors for Src, ERK, and JNK signalling pathways.The results show upregulation of NBCe1 mRNA level, protein abundance, and surface expression in hippocampal slices after 4‐AP treatment, effects that were abolished following inhibition of JNK signalling pathway. Increased membrane expression of NBCe1 was also prevented after inhibition of Src/ERK signalling. In cultured hippocampal and cortical astrocytes, 4AP treatment and extracellular alkalosis caused activation of astrocytes and increased surface NBCe1 protein.These data demonstrate regulation of NBCe1 transcript and surface expression, via Src/ERK and JNK signalling pathways.