Type II Na-P-i cotransport is regulated transcriptionally by ambient bicarbonate carbon dioxide tension in OK cells

The purpose of the present study was to determine whether isohydric changes in HCO3 concentration and Pco(2) directly affect apical Na-dependent P-i ( Na-P-i) cotransport in OK cells (opossum kidney cell Line). Cells were kept at either 44 mM NaHCO3/10% CO2, pH 7.4 (high-HCO3/CO2 condition), or 22 mM NaHCO3/5% CO2, pH 7.4 (low-HCO3/CO2 condition) (for 14-24 h). Incubation i n lower HCO3/CO2 concentrations increased Na-P-i cotransport 1.5-fold. The increased Na-P-i cotransport was paralleled by a two- to threefold increase d expression of the NaPi-4 transporter protein and a two- to threefold incr ease in NaPi-4 mRNA abundance. The increase in NaPi-4 mRNA could be complet ely prevented by incubation in the presence of a transcriptional inhibitor, suggesting that the increase in NaPi-4 mRNA results from an increased NaPi -4 mRNA transcription. In agreement, the NaPi-4 promoter activity was stimu lated by 50% at lower HCO3/CO2 concentrations. In conclusion, our data demo nstrate that isohydric changes in HCO3 concentration and Pco(2) exert a sig nificant, direct cellular effect on Na-P-i cotransport and NaPi-4 protein e xpression in OK cells by affecting NaPi-4 mRNA transcription.