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 PCO₂ 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 in 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 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.