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Glomerular permeability to macromolecules in the Necturus kidney

Tanner, George A.; Rippe, Catarina LU ; Shao, Youzhi; Evan, Andrew P. and Williams, James C., Jr. (2009) In American Journal of Physiology: Renal, Fluid and Electrolyte Physiology 296(6). p.1269-1278
Abstract
Tanner GA, Rippe C, Shao Y, Evan AP, Williams JC, Jr. Glomerular permeability to macromolecules in the Necturus kidney. Am J Physiol Renal Physiol 296: F1269-F1278, 2009. First published April 1, 2009; doi: 10.1152/ajprenal.00371.2007.-Many aspects of the glomerular filtration of macromolecules remain controversial, including the location of the major filtration barrier, the effects of electrical charge, and the reason the filtration barrier does not clog. We examined these issues in anesthetized Necturus maculosus, using fluorescently labeled probes and a two-photon microscope. With the high resolution of this system and the extraordinary width (similar to 3.5 mu m) of the glomerular basement membrane (GBM) in this salamander, we were... (More)
Tanner GA, Rippe C, Shao Y, Evan AP, Williams JC, Jr. Glomerular permeability to macromolecules in the Necturus kidney. Am J Physiol Renal Physiol 296: F1269-F1278, 2009. First published April 1, 2009; doi: 10.1152/ajprenal.00371.2007.-Many aspects of the glomerular filtration of macromolecules remain controversial, including the location of the major filtration barrier, the effects of electrical charge, and the reason the filtration barrier does not clog. We examined these issues in anesthetized Necturus maculosus, using fluorescently labeled probes and a two-photon microscope. With the high resolution of this system and the extraordinary width (similar to 3.5 mu m) of the glomerular basement membrane (GBM) in this salamander, we were able to visualize fluorescent molecules in the GBM in vivo. GBM/plasma concentration ratios for myoglobin, ovalbumin, and serum albumin did not differ from that of inulin, indicating that the GBM does not discriminate among these molecules. The GBM/plasma concentration ratios for fluoresceinated dextran 500 and 2,000 kDa were significantly below that of inulin. Glomerular sieving coefficients (GSCs) for various macromolecules decreased as molecular mass increased, and the GSCs for bovine or human serum albumin were extremely low. The effect of electrical charge on filterability of a macromolecule was also examined. The GSCs for native (anionic) and neutral human serum albumin were not significantly different, nor did GSCs for anionic and neutral dextran 40 kDa differ, indicating that charge has no detectable effect on filterability of these macromolecules. These studies indicate that the main filtration barrier to albumin is the podocyte slit diaphragm. Electron microscopic studies revealed many cell processes within the GBM. Macromolecules that penetrated the GBM were taken up by mesangial cells and endothelial cells, suggesting that these cells help to prevent clogging of the filter. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
amphibian kidney, glomerular filtration barrier, two-photon microscopy
in
American Journal of Physiology: Renal, Fluid and Electrolyte Physiology
volume
296
issue
6
pages
1269 - 1278
publisher
American Physiological Society
external identifiers
  • wos:000266342700006
  • scopus:66449104086
ISSN
0363-6127
DOI
10.1152/ajprenal.00371.2007
language
English
LU publication?
yes
id
11fa00e2-f410-4577-92f8-3263beaccec6 (old id 1425449)
date added to LUP
2009-07-02 10:32:49
date last changed
2017-12-11 11:30:59
@article{11fa00e2-f410-4577-92f8-3263beaccec6,
  abstract     = {Tanner GA, Rippe C, Shao Y, Evan AP, Williams JC, Jr. Glomerular permeability to macromolecules in the Necturus kidney. Am J Physiol Renal Physiol 296: F1269-F1278, 2009. First published April 1, 2009; doi: 10.1152/ajprenal.00371.2007.-Many aspects of the glomerular filtration of macromolecules remain controversial, including the location of the major filtration barrier, the effects of electrical charge, and the reason the filtration barrier does not clog. We examined these issues in anesthetized Necturus maculosus, using fluorescently labeled probes and a two-photon microscope. With the high resolution of this system and the extraordinary width (similar to 3.5 mu m) of the glomerular basement membrane (GBM) in this salamander, we were able to visualize fluorescent molecules in the GBM in vivo. GBM/plasma concentration ratios for myoglobin, ovalbumin, and serum albumin did not differ from that of inulin, indicating that the GBM does not discriminate among these molecules. The GBM/plasma concentration ratios for fluoresceinated dextran 500 and 2,000 kDa were significantly below that of inulin. Glomerular sieving coefficients (GSCs) for various macromolecules decreased as molecular mass increased, and the GSCs for bovine or human serum albumin were extremely low. The effect of electrical charge on filterability of a macromolecule was also examined. The GSCs for native (anionic) and neutral human serum albumin were not significantly different, nor did GSCs for anionic and neutral dextran 40 kDa differ, indicating that charge has no detectable effect on filterability of these macromolecules. These studies indicate that the main filtration barrier to albumin is the podocyte slit diaphragm. Electron microscopic studies revealed many cell processes within the GBM. Macromolecules that penetrated the GBM were taken up by mesangial cells and endothelial cells, suggesting that these cells help to prevent clogging of the filter.},
  author       = {Tanner, George A. and Rippe, Catarina and Shao, Youzhi and Evan, Andrew P. and Williams, James C., Jr.},
  issn         = {0363-6127},
  keyword      = {amphibian kidney,glomerular filtration barrier,two-photon microscopy},
  language     = {eng},
  number       = {6},
  pages        = {1269--1278},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Renal, Fluid and Electrolyte Physiology},
  title        = {Glomerular permeability to macromolecules in the Necturus kidney},
  url          = {http://dx.doi.org/10.1152/ajprenal.00371.2007},
  volume       = {296},
  year         = {2009},
}