A quantitative analysis of the glomerular charge barrier in the rat.
Modifying the ionic strength (I) is a gentle way to alter charge interactions, but it cannot be done for studies of the glomerular sieving of proteins in vivo. We therefore perfused 18 isolated rat kidneys with albumin solutions of different ionic strengths at a low temperature (cIPK) to inhibit tubular uptake and protease activity. Four anionic proteins were studied, namely albumin (Alb), orosomucoid (Oro), ovalbumin (Ova), and anionic horseradish peroxidase (aHRP), together with the neutral polymer Ficoll. With normal ionic strength of the perfusate (152 mM), the fractional clearance (theta) was 0.0018 +/- 0.0003 for Alb, 0.0033 +/- 0.0003 for Oro, 0.090 +/- 0.008 for Ova, and 0.062 +/- 0.002 for aHRP. These theta values were all lower than for Ficoll of similar hydrodynamic size; e.g., theta(Ficoll 36 A) was >20 times higher than theta for albumin. Low ionic strength (34 mM) increased size selectivity as theta for anionic proteins and Ficoll fell, suggesting a reduction in small-pore radius from 44 +/- 0.4 to 41 +/- 0.5 A, P < 0.01. In contrast, low I reduced the charge density of the membrane, omega, to one-quarter of the 20--50 meq/l estimated at normal I. These dynamic changes in omega seem to be due to volume alterations of the charged gel, fluid shifts that easily are accounted for by the changes in electroosmotic pressures. The finding that low ionic strength induces inverse effects on size selectivity and charge density strongly suggests that separate structures of the glomerular wall are responsible for the two properties.
Department of Physiology, Göteborg University, SE-405 30 Gothenburg, Sweden.
J
J
Sörensson
M
M
Ohlson
B
B
Haraldsson
D000418:Albumins / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D000838:Anions / Q000737:chemistry / Q000493:pharmacokinetics; D001692:Biological Transport / Q000502:physiology; D002199:Capillary Permeability / Q000502:physiology; D004563:Electrochemistry; D005260:Female; D005362:Ficoll / Q000737:chemistry / Q000493:pharmacokinetics; D006735:Horseradish Peroxidase / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000502:physiology*; D008954:Models, Biological; D008970:Molecular Weight; D009997:Osmotic Pressure; D010047:Ovalbumin / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar
D000418:Albumins; D000838:Anions; D005362:Ficoll; D010047:Ovalbumin; D006735:Horseradish Peroxidase