Type II Na-Pi 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 PCO2 directly affect apical Na-dependent Pi (Na-Pi) 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 in lower HCO3/CO2 concentrations increased Na-Pi cotransport 1.5-fold. The increased Na-Pi cotransport was paralleled by a two- to threefold increased expression of the NaPi-4 transporter protein and a two- to threefold increase in NaPi-4 mRNA abundance. The increase in NaPi-4 mRNA could be completely 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 stimulated by 50% at lower HCO3/CO2 concentrations. In conclusion, our data demonstrate that isohydric changes in HCO3 concentration and PCO2 exert a significant, direct cellular effect on Na-Pi cotransport and NaPi-4 protein expression in OK cells by affecting NaPi-4 mRNA transcription.