Tannic acid inhibits electrogenic Na+/HCO3− co-transporter activity in embryonic neural stem cell-derived radial glial-like cells

Self-renewing neural stem cells and progenitor cells are cell populations that generate radial glial cells and neurons through asymmetric division. Regulation of intracellular pH in stem cells with high metabolic activity is critical for both cell signaling and proliferation. We have recently found that a S0859-inhibitable electrogenic Na(+)/HCO(3)(−) co-transporter (NBCe1, Slc4a4), is the primary pH(i) regulatory mechanism in stem cell-derived radial glial-like cells. Here we show, by using the voltage-sensitive fluorescent dye DiBAC(4)(3) and BCECF, a pH-sensitive dye, that an antioxidant, tannic acid (100 µM), can inhibit potassium- and calcium-dependent rapid changes in membrane potential and NBCe1 mediated pH(i) regulation in brain-derived glial-like cells in vitro. Furthermore, neural stem cell differentiation and neurosphere formation (proliferation) were completely inhibited by tannic acid. The present study provides evidence that tannic acid is a natural inhibitor of NBCe1. It is tempting to speculate that tannic acid or related compounds that inhibits NBCe1-mediated pHi regulation in glial-like cells may also have bearing on the treatment of glial neoplasms.