NHE3 Na+/H+ exchanger supports proximal tubular protein reabsorption in vivo
Michael Gekle1, Katharina Völker, Sigrid Mildenberger
1Physiologisches Institut, Universität Würzburg, Germany. michael.gekle@mail.uni-wuerzburg.de
Abstract:
Proximal tubular receptor-mediated endocytosis (RME) of filtered proteins prevents proteinuria. Pharmacological and genetic studies in cultured opossum kidney cells have shown that the apical Na(+)/H(+) exchanger isoform 3 (NHE3) supports RME by interference with endosomal pH homeostasis and endocytic fusion events. However, it is not known whether NHE3 also supports proximal tubular RME in vivo. We analyzed proximal tubular protein reabsorption by microinfusion experiments in rats and investigated renal protein excretion in NHE3 knockout (Nhe3 -/-) mice. Inhibition of NHE3 by EIPA or S-3226 reduced the fractional reabsorption of [(14)C]cytochrome c by approximately 50% during early proximal microinfusion. During early distal microinfusion, no protein reabsorption could be detected. Urinary protein excretion of Nhe3 -/- or heterozygous mutant mice was significantly higher compared with wild-type mice. SDS-PAGE analysis of urinary proteins revealed that Nhe3 -/- animals excreted proteins the size of albumin or smaller. Thus a reduction in NHE3 activity or abundance causes tubular proteinuria. These data show that NHE3 supports proximal tubular RME of filtered proteins in vivo.
More Related Videos
11:51Application of Electrophysiology Measurement to Study the Activity of Electro-Neutral Transporters
Published on: February 3, 2018
07:06Isolation of Primary Human Proximal Tubule Epithelial Cells and Their Use in Creating a Microphysiological Model of the Renal Proximal Tubule
Published on: May 9, 2025
Related Concept Videos
Drug Elimination by Renal Route: Tubular Reabsorption
Reabsorption and Secretion in the Loop of Henle
Reabsorption and Secretion in the PCT
Transport mechanisms involving sodium ions (Na+) contribute significantly to solute reabsorption. These mechanisms include symport and antiport processes.
A key example is the...
Drug Elimination by Renal Route: Tubular Secretion
Physiology of the Genitourinary System II: Tubular Reabsorption and Secretion
Tubular Reabsorption and Secretion
Tubular reabsorption is a selective process that starts when the filtrate enters the proximal tubules. It involves substances traveling through the transcellular route (through the tubule cell and peritubular...
