Maturation of rabbit proximal straight  tubule chloride/base exchange

Shah, Mehul; Quigley, Raymond; Baum, Michel

doi:10.1152/ajprenal.1998.274.5.f883

Cited by 21 publications

(67 citation statements)

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“…We hypothesized that thyroid hormone was the most likely candidate causing these changes. We found that administration of thyroid hormone to neonatal rabbits using the same protocol as in the present study resulted in a premature maturation in passive chloride transport from zero to that comparable to the adult segment (5). We also studied adult rabbits that were made hypothyroid by administration of water that contained 0.1% propylthiouracil.…”

Section: Discussionmentioning

confidence: 60%

“…We recently demonstrated that adult rabbit proximal straight tubule perfused with a late proximal tubular fluid had a 50% reduction in the rate of volume absorption when active transport was inhibited by 10 −5 M of bath ouabain (4,5). The remaining half of chloride transport in this segment transport is passive and paracellular (6).…”

Section: Discussionmentioning

confidence: 99%

“…We have performed several physiologic studies pointing to a developmental change in paracellular permeability (4,5,8,33,34). Neonatal rabbit proximal tubules have a lower bicarbonate and chloride permeability than that of the adult segment (8,34).…”

Section: Discussionmentioning

confidence: 99%

“…active and transcellular and half is passive and paracellular (3)(4)(5). Active NaCl transport is mediated by the parallel operation of the Na+/H+ exchanger and a Cl−/base exchanger (3,4).…”

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Developmental Changes in Proximal Tubule Tight Junction Proteins

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We demonstrated previously that neonatal proximal tubules have a lower passive paracellular permeability to chloride ions and higher resistance than that of adult proximal tubules. In addition, administration of thyroid hormone to neonates, before the normal maturational increase in serum thyroid hormone levels, prematurely accelerates the developmental increase in chloride permeability to adult levels. To test the hypothesis that there is a maturational change in tight junction proteins and that thyroid hormone mediates these changes, we examined the two known tight junction proteins present in proximal tubules, occludin and claudin 2. Using immunoblot and immunohistochemistry, we demonstrated that claudin 2 has a 4-fold greater abundance in neonatal proximal tubules than in adult tubules. Occludin, however, has a 4-fold greater expression in adult tubules than in neonatal tubules. Administration of thyroid hormone to neonates did not affect claudin 2 expression, occludin expression, or the transepithelial resistance in rat proximal tubule cells in vitro. In conclusion, there are postnatal maturational changes in tight junction proteins. The factors that cause these maturational changes are unknown but unlikely to be due solely to the maturational increase in thyroid hormone.The proximal tubule receives an ultrafiltrate from the glomerulus and reabsorbs two thirds of the ultrafiltrate in a nearly iso-osmotic manner. In addition to active transcellular fluid transport, the proximal tubule reabsorbs solutes via passive diffusion across the paracellular pathway. The early proximal tubule reabsorbs glucose and amino acids and preferentially reabsorbs bicarbonate over chloride ions (1,2), which leaves the luminal fluid delivered to the late proximal tubule with a higher chloride concentration and lower bicarbonate concentration than that in the peritubular plasma (1,2). Passive solute transport is dependent on the gradients that develop between lumen and peritubular capillary and permeability properties of the paracellular pathway.Approximately two thirds of the filtered chloride is reabsorbed by the adult proximal tubule (1,3 active and transcellular and half is passive and paracellular (3-5). Active NaCl transport is mediated by the parallel operation of the Na+/H+ exchanger and a Cl−/base exchanger (3,4). Passive Cl absorption is mediated by diffusion of chloride ions down its concentration gradient generated in the early proximal tubule (6,7). Thus, the permeability properties of the paracellular pathway can affect a significant amount of proximal tubule NaCl transport.Furthermore, the permeability properties of the paracellular pathway serve as a barrier to prevent the back diffusion of glucose, amino acids, phosphate, bicarbonate, and other solutes that are in higher concentration in the peritubular fluid than in the lumen of the late proximal tubule. In previous in vitro rabbit microperfusion studies, our laboratory demonstrated that unlike the adult segment, the neonatal proximal tubule was impermeab...

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Developmental Changes in Proximal Tubule Tight Junction Proteins

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“…The Other solutes include (i) Cl Ϫ , (ii) organic solutes, and (iii) Na ϩ in excess of that accompanying HCO 3 Ϫ . Diffusion and solvent drag through tight junctions, possibly augmented by apical Cl-base exchange (34), could contribute to Cl Ϫ reabsorption (Fig. 3).…”

Section: Discussionmentioning

confidence: 99%

Evidence from renal proximal tubules that \documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy}\usepackage{mathrsfs}\setlength{\oddsidemargin}{-69pt}\begin{document}\begin{equation}{\mathrm{HCO}}_{3}^{-}\end{equation}\end{document} and solute reabsorption are acutely regulated not by pH but by basolateral \documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackag

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et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Respiratory acidosis, a decrease in blood pH caused by a rise in [CO 2], rapidly triggers a compensatory response in which the kidney markedly increases its secretion of H ؉ from blood to urine. However, in this and other acid-base disturbances, the equilibrium CO 2 kidney ͉ out-of-equilibrium solution ͉ acid-base disturbances ͉ volume reabsorption A major task of the kidney is to secrete H ϩ into the urine.Inadequate renal H ϩ secretion caused, for example, by mutations to acid-base transporters (1-4) or carbonic anhydrases (5), or by renal failure (6, 7), can lead to a life-threatening decrease in blood pH. Moreover, to maintain a stable blood pH, the kidney must appropriately increase H ϩ secretion in response to metabolic acidosis (a decrease in blood pH caused by a decrease in [HCO 3 Ϫ ] at a fixed CO 2 ) or to respiratory acidosis. However, a half century after the classical observation that respiratory acidosis rapidly stimulates renal H ϩ secretion (8, 9), we still have little insight into how the kidney senses acute acid-base disturbances.The renal proximal tubule (PT) reabsorbs (from lumen to blood) a liquid that contains Ϸ80% of the HCO 3 Ϫ filtered by the glomerulus. The PT cell does this reabsorbtion by secreting H ϩ into the PT lumen and using this H ϩ to titrate luminal HCO 3 Ϫ to CO 2 and H 2 O. After entering the cell across the apical membrane, the CO 2 and H 2 O recombine to produce H ϩ and HCO 3 Ϫ . The cell extrudes the H ϩ into the lumen across the apical membrane through Na-H exchangers (10-12) and H ϩ pumps (13) and moves the HCO 3 Ϫ out across the basolateral membrane via the electrogenic Na͞HCO 3 cotransporter NBCe1-A (14, 15). Carbonic anhydrases catalyze the interconversions between CO 2 and H 2 O on the one hand and HCO 3 Ϫ and H ϩ on the other (5). Because blood pH is the parameter regulated by these acid-base transport processes, blood pH or, more likely, intracellular pH (pH i ), has been thought to be the parameter sensed by renal cells. However, because of the interconversion CO 2 ϩ H 2 O^HCO 3 In the present study, we perfused single, isolated S2 segments of rabbit PTs and collected the fluid that had passed along the PT lumen. Analysis of this collected fluid allowed us to compute volume reabsorption (J V ); HCO 3 Ϫ reabsorption (J HCO 3 ), which is virtually the same as the H ϩ -secretion rate under the conditions of our experiments; and the reabsorption of solutes other than NaHCO 3 (J Other ). We made the surprising observation that, at least in the short term, J HCO 3 and J Other do not respond to changes in basolateral or intracellular pH. The most straightforward hypothesis is that PT cells have sensors for basolateral HCO 3 Ϫ and a parameter related to CO 2 . Materials and MethodsExcept for the compositions of most of the OOE CO 2 ͞HCO 3 Ϫ solutions, our methods are described in detail in ref. 17.Tubule Perfusion. We hand dissected kidneys from ''pathogenfree'' female New Zealand White rabbits (1.4-2.0 kg) to yield individual segments of midcortical S2 PTs in accorda...

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Renal Tubular Development

Baum

2014

Pediatric Nephrology

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The nephron is faced with the enormous task of maintaining a constant composition and volume of the extracellular fluid. The amount of electrolytes and water ingested and absorbed must be eliminated, and the waste products from metabolism must also be excreted. This challenge is all the more complex as our dietary intake is quite variable from day to day. Despite this variable intake, there is virtually no change in the volume or composition of the extracellular fluid volume from day to day.There are two possible ways that our kidney could balance ingestion and excretion. The kidney could be a secretory organ where all the excess solutes and water ingested would be excreted by tubular secretion. This would be very inefficient and require an enormous amount of energy. In addition, in times of a disturbance in the extracellular fluid volume such as a high salt intake or volume loss from diarrhea, the regulatory systems necessary to maintain a constant extracellular fluid volume and composition while excreting waste products would be very complex. On the other hand, the kidney could filter an enormous quantity of extracellular fluid, which would be very efficient in removing waste products, and reclaim the desired salt, organic solutes, and water. With volume depletion, a greater fraction of salt and water could be reabsorbed, and when one has a dietary indiscretion such as the salt intake from a pepperoni pizza, there could be a reduction in sodium reabsorption leading to an increase in excretion to bring us back into balance. The mammalian kidney actually uses both mechanisms to perform its job which is necessary for our survival on land. The adult kidney filters~150 l of isotonic fluid a day and reclaims most of it, leaving the waste produces to be excreted in about 1.5 l of urine. In addition, there are secretory processes for solutes such as organic anions and cations in the proximal tubule and secretory mechanisms to excrete the excess acid generated from metabolism in the distal nephron which aid in maintaining homeostasis.To accomplish the remarkable task of reclamation of the necessary solutes and water to maintain a constant composition of the extracellular fluid volume, the mammalian kidney has evolved into a highly specialized organ with thousands of units called nephrons. Each human kidney has approximately one million nephrons. Each nephron is a tube consisting of epithelial cells and is divided into 12 specialized segments as shown in Fig. 1. The epithelial cells allow for the vectorial transport of solutes. The proximal tubule is responsible for the bulk reclamation of solutes and water and for the secretion of organic cations and anions. Approximately two-thirds of the glomerular filtrate is reabsorbed by the proximal tubule in an isotonic fashion. Virtually all of the organic solutes, as well as the majority of bicarbonate, phosphate, and chloride, are reabsorbed in this segment. The proximal tubule is divided into S 1 , S 2 , and S 3 segments based on the rates of transport of some solutes and mor...

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Maturation of rabbit proximal straight tubule chloride/base exchange

Cited by 21 publications

References 25 publications

Developmental Changes in Proximal Tubule Tight Junction Proteins

Developmental Changes in Proximal Tubule Tight Junction Proteins

Renal Tubular Development

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