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.
Jehle
A W
AW
Institute of Physiology, University of Zurich-Irchel, CH-8057 Zurich, Switzerland.
Hilfiker
H
H
Pfister
M F
MF
Biber
J
J
Lederer
E
E
Krapf
R
R
Murer
H
H
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism* / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D009893:Opossums; D010281:Parathyroid Hormone / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000502:physiology; D017693:Sodium Bicarbonate / Q000494:pharmacology; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*
D001639:Bicarbonates; D002352:Carrier Proteins; D005938:Glucocorticoids; D019384:Nucleic Acid Synthesis Inhibitors; D010281:Parathyroid Hormone; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters; D002245:Carbon Dioxide; D004004:Dichlororibofuranosylbenzimidazole; D003907:Dexamethasone; D017693:Sodium Bicarbonate