scholarly journals In developing mouse kidneys, orientation of loop of Henle growth is adaptive and guided by long‐range cues from medullary collecting ducts

2019 ◽  
Vol 235 (2) ◽  
pp. 262-270 ◽  
Author(s):  
C‐Hong Chang ◽  
Jamie A. Davies
1996 ◽  
Vol 270 (4) ◽  
pp. F604-F613 ◽  
Author(s):  
J. R. Asplin ◽  
N. S. Mandel ◽  
F. L. Coe

We have used published rat micropuncture data to construct a matrix of ion concentrations along the rat nephron. With an iterative computer model of known ion interactions, we calculated relative supersaturation ratios in all nephron segments. The collecting ducts and urine showed expected supersaturation with stone-forming salts. Fluid in the thin segment of the loop of Henle may be supersaturated with calcium carbonate and calcium phosphate under certain conditions. Because calculations cannot predict the actual course of crystallization, we made solutions to mimic, in vitro, presumed conditions in the loop of Henle. The solid phases that formed were analyzed by X-ray powder diffraction, electron microprobe, and infrared spectroscopy. All samples were identified as poorly crystallized or immature apatite. The descending limb of Henle's loop creates a unique condition as it extracts water but not sodium, bicarbonate, calcium, or phosphate, giving a calcium concentration at the bend of 3 mM, pH 7.4, and a phosphate concentration that varies from 0.8 to 48 mM, depending on parathyroid hormone and dietary phosphate. We conclude that conditions in the thin segment potentially could create a solid calcium phosphate phase, which may initiate nucleation of calcium oxalate salts in the collecting ducts, potentiating nephrolithiasis and nephrocalcinosis.


1960 ◽  
Vol 198 (3) ◽  
pp. 581-585 ◽  
Author(s):  
Carl W. Gottschalk ◽  
William E. Lassiter ◽  
Margaret Mylle

Fluid was collected by micropuncture from individual renal tubules of anesthetized rats and its pH determined with the quinhydrone microelectrode. The single glomerular sample and early proximal fluid were isohydric with arterial blood, but later proximal fluid usually showed progressive acidification. The maximum proximal fall in pH was 0.43 u in nondiuretic rats, 0.56 u during profuse glucose or mannitol diuresis, and 0.78 u in rats previously loaded with ammonium chloride and undergoing glucose diuresis. Fluid from the early distal convolution was usually acidified relative to arterial blood but was not significantly different from late proximal fluid. Progressive acidification probably also occurred in the distal convolution. The pH decreased further in the collecting ducts, much more so in the nondiuretic state than during diuresis. The quantitative importance of proximal reabsorption of HCO3– and, by inference, H+ secretion is emphasized. It is suggested that the pH of tubular fluid may increase in the thin descending limb of the loop of Henle, especially in a kidney elaborating a concentrated urine, because of increased concentration of HCO3–.


1987 ◽  
Vol 252 (3) ◽  
pp. F491-F500 ◽  
Author(s):  
D. W. Good ◽  
C. R. Caflisch ◽  
T. D. DuBose

Transport of NH3 from loops of Henle to medullary collecting ducts has been proposed to play an important role in renal ammonia excretion. To determine whether transepithelial ammonia concentration gradients capable of driving this transport are present in the inner medulla, micropuncture experiments were performed in control rats and in rats with chronic metabolic acidosis. In situ pH and total ammonia concentrations were measured to calculate NH3 concentrations ([NH3]) for base and tip collecting duct, loop of Henle, and vasa recta. In control and acidotic rats, [NH3] in the loop of Henle was significantly greater than [NH3] in the collecting ducts. [NH3] did not differ in loop of Henle and adjacent vasa recta in either group of rats, indicating that NH3 concentration gradients between loop and collecting duct represent NH3 gradients that are present between medullary interstitium and collecting duct. During acidosis, an increase in collecting duct ammonia secretion was associated with an increase in the NH3 concentration difference between loop of Henle and collecting duct but occurred in the absence of a fall in collecting duct pH. The NH3 concentration gradient favoring diffusion of NH3 into the collecting ducts increased during acidosis because [NH3] in the loop of Henle and medullary interstitium increased more than [NH3] in the collecting duct. These findings indicate that transport processes involved in medullary ammonia accumulation play an important role in regulating ammonia secretion into the inner medullary collecting duct in vivo and that a fall in inner medullary collecting duct pH is not necessarily required for ammonia secretion by this segment to increase during chronic metabolic acidosis.


2000 ◽  
Vol 279 (6) ◽  
pp. F1139-F1160 ◽  
Author(s):  
H. E. Layton ◽  
John M. Davies ◽  
Giovanni Casotti ◽  
Eldon J. Braun

A mathematical model was used to investigate how concentrated urine is produced within the medullary cones of the quail kidney. Model simulations were consistent with a concentrating mechanism based on single-solute countercurrent multiplication and on NaCl cycling from ascending to descending limbs of loops of Henle. The model predicted a urine-to-plasma (U/P) osmolality ratio of ∼2.26, a value consistent with maximum avian U/P osmolality ratios. Active NaCl transport from descending limb prebend thick segments contributed 70% of concentrating capability. NaCl entry and water extraction provided 80 and 20%, respectively, of the concentrating effect in descending limb flow. Parameter studies indicated that urine osmolality is sensitive to the rate of fluid entry into descending limbs and collecting ducts at the cone base. Parameter studies also indicated that the energetic cost of concentrating urine is sensitive to loop of Henle population as a function of medullary depth: as the fraction of loops reaching the cone tip increased above anatomic values, urine osmolality increased only marginally, and, ultimately, urine osmolality decreased.


1997 ◽  
Vol 272 (6) ◽  
pp. R2004-R2008 ◽  
Author(s):  
D. D. Fanestil ◽  
D. A. Vaughn ◽  
P. Blakely

The renal responses to metabolic acidosis/alkalosis involve changes in the proximal tubule, loop of Henle, and collecting ducts. We tested for acid- or base-induced changes in the distal convoluted tubule (DCT) by examining the renal density of the DCT's receptor for thiazide-type diuretics (TZR), as estimated by the binding of [3H]metolazone in Wistar-Kyoto rats. TZR density significantly decreased by 17% in rats ingesting NH4Cl for 3.5 days and by nearly 30% after 7 days; TZR increased up to 40% in rats ingesting NaHCO3 for 2-4 days but was no longer significantly increased after 7 days. Urinary excretion of chloride increased as renal density of the TZR decreased, a finding consistent with the interpretation that acidosis/alkalosis not only altered TZR density but coordinately altered reabsorption of NaCl by the thiazidesensitive Na-Cl cotransporter. The result is that delivery of Na from DCT is enhanced during acidosis and decreased during alkalosis, assisting in compensatory changes in distal nephron secretion of hydrogen ion. The integrated renal response to metabolic acidosis/alkalosis involves a decrease in renal TZR with acidosis and an increase in TZR with alkalosis.


2000 ◽  
Vol 279 (5) ◽  
pp. R1722-R1730 ◽  
Author(s):  
Giovanni Casotti ◽  
Kimberly K. Lindberg ◽  
Eldon J. Braun

The organization of the renal medulla of the Gambel's quail, Callipepla gambelii, kidney was examined to determine the number of loops of Henle and collecting ducts and the surface area occupied by the different nephron segments as a function of distance down the medullary cones. Eleven medullary cones were dissected from the kidneys of four birds, and the tissue was processed and sectioned for light microscopy. In addition, individual nephrons were isolated on which total loop thin descending segment and thick prebend segment lengths were measured. The results show no correlation between the absolute number of loops of Henle and the length of the medullary cones. The number of thick and thin limbs of Henle and collecting ducts decrease exponentially with distance toward the apex of the cones and the rate of decrease is similar for cones of different lengths. Initially there is a rapid decrease in the number of thin limbs of Henle, indicating that most nephrons do not penetrate the cones a great distance. Thick descending limbs of Henle (prebend segment) ranged in length from 50 to 770 μm, and there was little correlation with the total length of the loop of Henle. However, the length of the thin limb of Henle correlated well with total loop length. The cell surface areas of the limbs of the loop of Henle and the collectng ducts decreased toward the apex of the cones.


1991 ◽  
Vol 2 (6) ◽  
pp. 1122-1129 ◽  
Author(s):  
R J Bindels ◽  
J A Timmermans ◽  
A Hartog ◽  
W Coers ◽  
C H van Os

There is strong evidence that vitamin D-dependent Ca(2+)-binding proteins, i.e., calbindin-D9k and calbindin-D28k, facilitate diffusion of Ca2+ through the cytosolic compartment of renal and intestinal cells, which transport Ca2+ transcellularly. In the study presented here, parvalbumin, calbindin-D9k, and calbindin-D28k were localized precisely by immunocytochemistry in rat kidney. Antisera recognizing specifically the thick ascending loop of Henle, the connecting tubules and collecting ducts, and the intercalated cells of the collecting ducts were used to identify different cell types. In rat kidney cortex, parvalbumin and calbindin-D9k colocalized in the thick ascending loop of Henle, the distal convoluted tubule, the connecting tubule, and the intercalated cells of the collecting duct. Strikingly, in all responsive cells, parvalbumin and calbindin-D9k were exclusively present in a thin layer along the basolateral membrane. In contrast, calbindin-D28k was only present in the distal convoluted and connecting tubule, where it was evenly distributed through the cytosol. In conclusion, the exclusive localization of parvalbumin and calbindin-D9k at the basolateral membrane of immunopositive renal cells implies their involvement in the regulation of transport processes located in these membranes rather than a role as intracellular Ca2+ buffer and Ca2+ shuttle between the two opposing membranes.


2016 ◽  
Vol 39 (1) ◽  
pp. 172-182 ◽  
Author(s):  
Liudmila Cebotaru ◽  
Valeriu Cebotaru ◽  
Hua Wang ◽  
Lois J. Arend ◽  
William B. Guggino

Background/AIM: STIM1 is as an essential component in store operated Ca2+ entry. However give the paucity of information on the role of STIM1 in kidney, the aim was to study the function of STIM1 in the medulla of the kidney. Methods: we crossed a Ksp-cre mouse with another mouse containing two loxP sites flanking Exon 6 of STIM1. The Ksp-cre mouse is based upon the Ksp-cadherin gene promoter which expresses cre recombinase in developing nephrons, collecting ducts (SD) and thick ascending limbs (TAL) of the loop of Henle. Results: The offspring of these mice are viable without gross morphological changes, however, we noticed that the STIM1 Ksp-cre knockout mice produced more urine compared to control. To examine this more carefully, we fed mice low (LP) and high protein (HP) diets respectively. When mice were fed HP diet STIM1 ko mice had significantly increased urinary volume and lower specific gravity compared to wt mice. In STIM1 ko mice fed HP diet urine creatinine and urea were significantly lower compared to wt mice fed HP diet, however the fractional excretion was the same. Conclusion: These data support the idea that STIM1 ko mice have impaired urinary concentrating ability when challenged with HP diet is most likely caused by impaired Ca2+-dependent signal transduction through the vasopressin receptor cascade.


1972 ◽  
Vol 20 (2) ◽  
pp. 89-96 ◽  
Author(s):  
ARUN K. ROY ◽  
DOUGLAS L. RABER

α2u-Globulin is an androgen-inducible rat urinary protein of hepatic origin. Examination of adult male rat liver sections with rhodamine-labeled anti-α2u-antiserum showed that the liver parenchymal cells are the site of α2u-globulin synthesis and that all of the parenchymal cells contain this protein. Immunofluorescent localization of α2u-globulin in male kidney sections revealed the existence of the protein in the cells of proximal convoluted tubules, in the loop of Henle as well as in the distal convoluted tubule. The collecting ducts did not bind the fluorescent labeled antibody. Intraperitoneally administered rhodamine-labeled α2u-globulin was found to be localized only in the kidney tubules in particulate form. It is concluded that α2u-globulin after its synthesis and release from the hepatic parenchymal cells is filtered into the renal tubular lumen and that both kinds of convoluted tubules as well as the loop of Henle are actively involved in α2u reabsorption.


2002 ◽  
Vol 283 (4) ◽  
pp. F817-F825 ◽  
Author(s):  
R. A. Fenton ◽  
G. S. Stewart ◽  
B. Carpenter ◽  
A. Howorth ◽  
E. A. Potter ◽  
...  

Specialized transporter proteins that are the products of two closely related genes, UT-A ( Slc14a2) and UT-B ( Slc14a1), modulate the movement of urea across cell membranes. The purpose of this study was to characterize the mouse variants of two major products of the UT-A gene, UT-A1 and UT-A2. Screening a mouse kidney inner medulla cDNA library yielded 4,047- and 2,876-bp cDNAs, the mouse homologues of UT-A1 and UT-A2. Northern blot analysis showed high levels of UT-A mRNAs in kidney medulla. UT-A transcripts were also present in testes, heart, brain, and liver. Immunoblots with an antiserum raised to the 19 COOH-terminal amino acids of rat UT-A1 (L194) identified immunoreactive proteins in kidney, testes, heart, brain, and liver and showed a complex pattern of differential expression. Relative to other tissues, kidney and brain had the highest levels of UT-A protein expression. In kidney sections, immunostaining with L194 revealed immunoreactive proteins in type 1 (short) and type 3 (long) thin descending limbs of the loop of Henle and in the middle and terminal inner medullary collecting ducts. Expression in Xenopus laevis oocytes showed that, characteristic of UT-A family members, the cDNAs encoded phloretin-inhibitable urea transporters. Acute application of PKA agonists (cAMP/forskolin/IBMX) caused a significant increase in UT-A1- and UT-A3-, but not UT-A2-mediated, urea transport.


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