Differential regulation of the renal sodium-phosphate cotransporters NaPi-IIa, NaPi-IIc, and PiT-2 in dietary potassium deficiency

• DOI: 10.1152/ajprenal.90765.2008
• Publication Date: 2009-06-03T20:45:37Z
• Authors: Sophia Y. Breusegem; Hideaki Takahashi; Hector Giral-Arnal; Xiaoxin Wang; Tao Jiang; Jill W. Verlander; Paul Wilson; Shinobu Miyazaki-...; Eileen Sutherland; Yupanqui Caldas; Judith T. Blaine; Hiroko Segawa; Ken-ichi Miyamoto; Nicholas P. Barry; Moshe Levi
• Keywords: Male; 0301 basic medicine; Microvilli; Hypophosphatemia; Sodium-Phosphate Cotransporter Proteins, Type III; Cell Membrane; Cytoplasmic Vesicles; Biological Transport; Articles; Kidney; Sodium-Phosphate Cotransporter Proteins, Type IIa; Rats; Mice, Inbred C57BL; Rats, Sprague-Dawley; Disease Models, Animal; Mice; Protein Transport; 03 medical and health sciences; Gene Expression Regulation; Animals; Phosphorus, Dietary; RNA, Messenger; Potassium Deficiency

Dietary potassium (K) deficiency is accompanied by phosphaturia and decreased renal brush border membrane (BBM) vesicle sodium (Na)-dependent phosphate (Pi) transport activity. Our laboratory previously showed that K deficiency in rats leads to increased abundance in the proximal tubule BBM of the apical Na-Pi cotransporter NaPi-IIa, but that the activity, diffusion, and clustering of NaPi-IIa could be modulated by the altered lipid composition of the K-deficient BBM (Zajicek HK, Wang H, Puttaparthi K, Halaihel N, Markovich D, Shayman J, Beliveau R, Wilson P, Rogers T, Levi M. Kidney Int 60: 694–704, 2001; Inoue M, Digman MA, Cheng M, Breusegem SY, Halaihel N, Sorribas V, Mantulin WW, Gratton E, Barry NP, Levi M. J Biol Chem 279: 49160–49171, 2004). Here we investigated the role of the renal Na-Pi cotransporters NaPi-IIc and PiT-2 in K deficiency. Using Western blotting, immunofluorescence, and quantitative real-time PCR, we found that, in rats and in mice, K deficiency is associated with a dramatic decrease in the NaPi-IIc protein abundance in proximal tubular BBM and in NaPi-IIc mRNA. In addition, we documented the presence of a third Na-coupled Pi transporter in the renal BBM, PiT-2, whose abundance is also decreased by dietary K deficiency in rats and in mice. Finally, electron microscopy showed subcellular redistribution of NaPi-IIc in K deficiency: in control rats, NaPi-IIc immunolabel was primarily in BBM microvilli, whereas, in K-deficient rats, NaPi-IIc BBM label was reduced, and immunolabel was prevalent in cytoplasmic vesicles. In summary, our results demonstrate that decreases in BBM abundance of the phosphate transporter NaPi-IIc and also PiT-2 might contribute to the phosphaturia of dietary K deficiency, and that the three renal BBM phosphate transporters characterized so far can be differentially regulated by dietary perturbations.