Submitted on April 18, 2007
Accepted on August 23, 2007
Evidence for restriction of fluid and solute movement across the glomerular capillary wall by the sub podocyte space
Andrew HJ Salmon1, Ildiko Toma2, Arnold Sipos3, Robert Muston1, Steven J. Harper1, David O. Bates1, Christopher R. Neal4, and Janos Peti-Peterdi5*
1 Department of Physiology, University of Bristol, Bristol, United Kingdom
2 Department of Physiology, University of Southern California, Los Angeles, California, United States
3 Physiology and Biophysics, University of Southern California, Los Angeles, California, United States
4 University of Bristol; University of Bristol, United States
5 Dept. of Physiology & Biophysics, Univ. Southern California, Los Angeles, California, United States
* To whom correspondence should be addressed. E-mail: petipete{at}usc.edu.
The glomerular filtration barrier (GFB) is generally considered to consist of three layers: fenestrated glomerular endothelium, glomerular basement membrane, and filtration slits between adjacent podocyte foot processes. Detailed anatomical examination of the GFB has revealed a novel abluminal structure, the sub-podocyte space (SPS), identified as the labyrinthine space between the underside of podocyte cell body/primary processes and the foot processes. The SPS covers 50-65% of the filtration surface of the GFB, indicating that SPS may influence glomerular permeability. We have examined the contribution of the SPS to the permeability characteristics of the GFB using multiphoton microscopy techniques in isolated perfused glomeruli and in the intact kidney in vivo. SPS were identified using this technique, with comparable dimensions to SPS examined with electron microscopy. The passage of the intermediate weight molecule rhodamine-conjugated 10kDa-dextran, but not the low weight molecule Lucifer yellow (
450 Da), accumulated in SPS-covered regions of the GFB, as compared with GFB regions not covered by SPS ("naked regions"). Net Lucifer Yellow flux (taken to indicate fluid flux) through identifiable SPS regions was calculated to be 66 - 75% of that occurring through naked regions. These observations indicate both ultrafiltration and hydraulic resistance imparted by the SPS, demonstrating the potential physiological contribution of the SPS to glomerular permeability.
