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This Article Full Text Full Text (PDF) All Versions of this Article: 293/6/F1777    most recent 00187.2007v2 00187.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Salmon, A. H. J. Articles by Peti-Peterdi, J. Search for Related Content PubMed PubMed Citation Articles by Salmon, A. H. J. Articles by Peti-Peterdi, J.

Evidence for restriction of fluid and solute movement across the glomerular capillary wall by the subpodocyte space

¹Microvascular Research Laboratories, Bristol Heart Institute, Department of Physiology, University of Bristol, ²Academic Renal Unit, Clinical Science at North Bristol, University of Bristol, Paul O'Gorman Lifeline Centre, Southmead Hospital, Westbury-on-Trym, Bristol, United Kingdom; and ³Departments of Physiology, Biophysics, and Medicine, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California

Submitted 18 April 2007 ; accepted in final form 23 August 2007

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 anatomic examination of the GFB has revealed a novel abluminal structure, the subpodocyte 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 10-kDa dextran, but not the low-weight molecule lucifer yellow (450 Da), accumulated in SPS-covered regions of the GFB, 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.

glomerulus; permeability; podocyte; multiphoton