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

Am J Physiol Renal Physiol. 2009 Aug;297(2):F350-61. doi: 10.1152/ajprenal.90765.2008. Epub 2009 Jun 3.

Abstract

Dietary potassium (K) deficiency is accompanied by phosphaturia and decreased renal brush border membrane (BBM) vesicle sodium (Na)-dependent phosphate (P(i)) transport activity. Our laboratory previously showed that K deficiency in rats leads to increased abundance in the proximal tubule BBM of the apical Na-P(i) 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-P(i) 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 P(i) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Cell Membrane / metabolism
  • Cytoplasmic Vesicles / metabolism
  • Disease Models, Animal
  • Gene Expression Regulation
  • Hypophosphatemia / metabolism
  • Kidney / metabolism*
  • Kidney / ultrastructure
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microvilli / metabolism
  • Phosphorus, Dietary / blood
  • Phosphorus, Dietary / metabolism*
  • Phosphorus, Dietary / urine
  • Potassium Deficiency / genetics
  • Potassium Deficiency / metabolism*
  • Protein Transport
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Phosphate Cotransporter Proteins, Type III / genetics
  • Sodium-Phosphate Cotransporter Proteins, Type III / metabolism*
  • Sodium-Phosphate Cotransporter Proteins, Type IIa / genetics
  • Sodium-Phosphate Cotransporter Proteins, Type IIa / metabolism*
  • Sodium-Phosphate Cotransporter Proteins, Type IIc / genetics
  • Sodium-Phosphate Cotransporter Proteins, Type IIc / metabolism*

Substances

  • Phosphorus, Dietary
  • RNA, Messenger
  • Slc20a2 protein, mouse
  • Slc20a2 protein, rat
  • Slc34a1 protein, mouse
  • Slc34a1 protein, rat
  • Slc34a3 protein, mouse
  • Slc34a3 protein, rat
  • Sodium-Phosphate Cotransporter Proteins, Type III
  • Sodium-Phosphate Cotransporter Proteins, Type IIa
  • Sodium-Phosphate Cotransporter Proteins, Type IIc