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H R Jacobson

Publications and source records attributed to H R Jacobson.

80 records · Page 5Linked to original sources

Determination of chloride and bicarbonate permeabilities in proximal convoluted tubules.

In late proximal tubules volume reabsorption linked to passive ion flows relies on the existence of differing permeability coefficients to Cl- and HCO3(-) (PCl greater than PHCO3). We measured these permeability coefficients in late segments of rabbit superficial (SFPCT) and juxtamedullary (JMPCT) proximal convoluted tubules perfused in vitro. PHCO3 and P36Cl were determined in tubules bathed in rabbit serum and perfused with a serum ultrafiltrated titrated with H2SO4 to [HCO3(-)] of 4 mM. Active transport, transepithelial voltage, and HCO3(-) reabsorption were inhibited by cooling (21 degrees C) and 10(-4) M acetazolamide. P36Cl and PHCO3 were calculated from 36Cl disappearance from and total CO2 addition to the perfusate. P36Cl in SFPCT was twice that in JMPCT but PHCO3 was the same in both segments. P36Cl exceeded PHCO3 only in SFPCT. To exclude exchange diffusion from contributing to P36Cl, additional tubules were perfused with ultrafiltrate titrated with HCl.P36Cl and simultaneously measured PCl (lumen-to-bath net chemical Cl- flux) were identical. We conclude: 1) SFPCT and JMPCT are heterogeneous with respect to Cl- permeability; 2) relative Cl--to-HCO3(-) permeabilities predict that anion gradients present in late portions of proximal tubules would support more volume reabsorption linked to passive ion flows in SF than in JMPCT; 3) no significant Cl- exchange diffusion exists in proximal tubules.

Absorption↗

Characteristics of volume reabsorption in rabbit superficial and juxtamedullary proximal convoluted tubules.

Segments of superficial and juxtamedullary proximal convoluted tubules of the rabbit were perfused in vitro to examine the mechanisms responsible for net volume reabsorption. The very early postglomerular segments were not studied. Fluid reabsorptive rates and transepithelial potential differences were compared under various conditions: (a) with perfusate that simulated glomerular filtrate; (b) with perfusate that lacked glucose, amino acids, and acetate and that had HCO(3) and Cl concentrations of 5 and 140 mM, respectively; (c) with perfusate that lacked glucose, amino acids, and acetate but with 20 meq of NaHCO(3) replaced with 20 meq of Na cyclamate; (d) with the same perfusate as in b but in the presence of ouabain in the bath; (e) with ultrafiltrate of rabbit serum titrated with HCl to final HCO(3) and Cl concentrations of 2 and 134 mM, respectively. Tubules were perfused with this titrated ultrafiltrate at 37 degrees C, 21 degrees C, and in the presence of 0.1 mM ouabain in the bath. Bath fluid in all experiments was regular rabbit serum. Under conditions a and b superficial proximal convoluted tubule (SFPCT) and juxtamedullary proximal convoluted tubule (JMPCT) behaved similarly with the exception that SFPCT exhibited a lumen-positive and JMPCT a lumen-negative electrical potential under condition b. However, under condition c SFPCT failed to exhibit net volume reabsorption, whereas reabsorption in JMPCT continued unchanged. Ouabain did not affect volume reabsorption in SFPCT under condition d, whereas neither ouabain nor hypothermia affected SFPCT under condition e. In contrast, ouabain and hypothermia totally inhibited volume reabsorption in JMPCT under conditions d and e. These studies document heterogeneous mechanisms responsible for volume reabsorption in the major portions of SFPCT and JMPCT with passive forces predominating in SFPCT and active forces in JMPCT.

Absorption↗

Intrinsic differences in various segments of the proximal convoluted tubule.

Until recently it has not been possible to compare directly the function of superficial and juxtamedullary nephrons. The present studies, using in vitro microperfusion, were designed to examine whether functional differences exist between proximal convoluted tubule segments of superficial and juxtamedullary nephrons. Electrophysiological studies showed that major differences exist between the relative chloride and sodium permeabilities of these segments. In the 1st mm of the superficial proximal convoluted tubule, the permeability to sodium was greater than that to chloride, whereas in the 2nd mm of the superficial proximal convoluted tubule and all later segments, the permeability to chloride was greater than that to sodium. The juxtamedullary proximal convoluted tubule was found to differ from the superficial proximal convoluted tubule in two respects: first, the relative permeabilities to chloride and sodium did not differ in the various segments of the juxtamedullary proximal convoluted tubule; second, the permeability to sodium was greater than to chloride throughout. When perfused with a solution lacking glucose and amino acids, the superficial and juxtamedullary convolutions exhibited the same transepithelial potential change, a reversible decrease to less than -- 1 mV. It thus appears that in both convolutions there exists electrogenic sodium transport coupled to the transport of these organic solutes. This differs from pars recta of both of these nephrons, which have been shown to exhibit electrogenic sodium transport independent of organic solutes. However, when perfused with a solution lacking glucose and amino acids but also containing high chloride and low bicarbonate concentrations, the superficial convolution developed a significantly more positive potential than the juxtamedullary. This difference reflects greater relative chloride permeability in the superficial proximal convolution. These studies show that intrinsic functional differences exist between proximal convoluted tubules obtained from the superficial and juxtamedullary nephron populations.

Alanine↗

Electrophysiological study of isolated perfused human collecting ducts: Ion dependency of the transepithelial potential difference.

Cortical and outer medullary collecting duct segments were dissected from human kidneys and perfused in vitro. The transepithelial potential difference was measured and found to be lumen positive +6.8 +/- 0.6 mV (n= 20). This lumen-positive potential difference was inhibited by ouabain and furosemide but not by acetazolamide. Replacement of chloride in bath and perfusion fluids caused a reversible decrease of the potential difference to near zero. We conclude from these studies: (a) the lumen-positive potential difference is dependent upon the presence of chloride ion suggesting the existence of an active electrogenic chloride reabsorptive process in the human collecting duct and (b) it is possible to examine human renal physiology directly using in vitro microperfusion of tubule segments.

Acetazolamide↗