Recently, we discovered that some of the fluid which filters across the glomerular filtration barrier (GFB) must enter restrictive spaces under the podocyte (SPS) (Neal et al). Fluid then enters interpodocyte spaces (IPS) draining fluid to the capillary tuft edge and into the peripheral urinary space (PUS) and hence the proximal convoluted tubule (PCT). We have now investigated the effects of increased perfusion pressure on these divisions of urinary space. Kidneys from rats humanely killed in accordance with UK guidelines were either immersion fixed (n=3, renal arterial pressure of 0mmHg) or perfusion fixed immediately after cervical dislocation with glutaraldehyde after a flush through with Ringer solution (n=5, renal arterial pressure of 100mmHg throughout). Kidney pieces were postfixed, dehydrated, embedded and serial ultrathin sections of glomeruli were cut. Regions of the capillary tuft were reconstructed from electron micrographs. In glomerular sections the SPS and IPS were measured, reconstructed and compared between groups (mean±SEMs compared by unpaired Student’s t-tests) In immersion and perfusion fixed glomeruli the coverage of the GFB by the SPS was not significantly different (60±3%. v 57±5%). The SPS height frequency distribution showed that perfusion fixed podocytes were more closely opposed to the GFB in some regions and raised in others compared with immersion fixed podocytes. However, the SPS exit pores became narrower with perfusion fixation (0.21±0.02μm, n=7 v. 0.33±0.04μm, n=6; p<0.05) and the area of attachment of processes anchoring the podocyte onto the GFB more than doubled with perfusion fixation (11±6%, n=3; 26±2%, n=5; p<0.05). The IPS doubles in width with perfusion fixation (0.74±0.06μm, n=29; 1.38±0.19μm, n=12; p0.05). The podocytes that cover the SPS respond to perfusion fixation and its supernormal filtration by increasing the anchorage area to the GFB, narrowing the SPS exit pores and ‘clamping down’ onto the GFB. Although the IPS gets wider with increased filtration, at the capillary tuft edge, the IPS stays narrow before widening into the PUS suggesting podocytic control at the edge of the tuft. The podocytes appear capable of rapid individual and global responses to changes in filtration pressure and/or flow, altering the characteristics of two of the three urinary spaces within Bowman’s capsule.
King's College London (2005) J Physiol 565P, C12
Communications: Urinary space reconstruction shows three subdivisions in which increased perfusion pressure induces a complex rapid podocytic response
Neal, Chris Robert; Bell, E ; Crook, H ; Bates, DO ; Harper, SJ ;
1. Department of Physiology, University of Bristol , Bristol, United Kingdom.
View other abstracts by:
Where applicable, experiments conform with Society ethical requirements.