Differential trafficking of NaPi2a and NaPi2c in response to PTH at the apical surface of renal proximal tubular cells

Abstract

Disordered phosphorous homeostasis is a significant cause of cardiovascular morbidity and mortality. Parathyroid hormone (PTH) is a critical regulator of phosphorous homeostasis and the kidney plays a crucial role in maintaining phosphorous balance. Renal excretion of phosphorous is controlled by the sodium phosphate cotransporters NaPi2a and NaPi2c. The goal of this study is to examine the mechanisms governing the differential regulation of renal NaPi2a and NaPi2c in response to PTH. Using a novel application of total internal reflection fluorescence microscopy (TIR‐FM) to the apical membrane of renal proximal tubular cells we have found that, in response to PTH, NaPi2a is removed from the apical surface 3 times faster than NaPi2c. These findings have been confirmed using more traditional methods such as confocal microscopy and Western blot analysis. The advantage of TIR‐FM is that it allows selective examination of the apical surface of cells. We are currently using this technique to examine the role of apical brush border components including actin and myosin VI to the differential regulation of NaPi2a and NaPi2c by PTH. Funded by American Heart Association SDG 0830394N.