Differential effects of ADH on sodium, chloride, potassium, calcium and magnesium transport in cortical and medullary thick ascending limbs of mouse nephron

Wittner, Monika; Stefano, Antonio Di; Wangemann, P.; Nitschke, Roland; Greger, R.; Bailly, Claire; Amiel, Catherine; Roinel, N.; Rouffignac, C. de

doi:10.1007/bf00582541

Cited by 93 publications

(50 citation statements)

References 30 publications

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“…Interestingly, one study showed that the presence of bicarbonate enhances the mTAL Ca 2ϩ flux (42), whereas most perfusion studies are performed in the absence of HCO 3 Ϫ . Based on flux measurements, we assumed here that the mTAL permeability to Ca 2ϩ is one tenth that of the cTAL.…”

Section: Calcium Reabsorption In the Talmentioning

confidence: 99%

A model of calcium transport along the rat nephron

Tournus

Seguin

Perthame

et al. 2013

American Journal of Physiology-Renal Physiology

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(Ca 2ϩ ) transport along the rat nephron to investigate the factors that promote hypercalciuria. The model is an extension of the flat medullary model of Hervy and Thomas (Am J Physiol Renal Physiol 284: F65-F81, 2003). It explicitly represents all the nephron segments beyond the proximal tubules and distinguishes between superficial and deep nephrons. It solves dynamic conservation equations to determine NaCl, urea, and Ca 2ϩ concentration profiles in tubules, vasa recta, and the interstitium. Calcium is known to be reabsorbed passively in the thick ascending limbs and actively in the distal convoluted (DCT) and connecting (CNT) tubules. Our model predicts that the passive diffusion of Ca 2ϩ from the vasa recta and loops of Henle generates a significant axial Ca 2ϩ concentration gradient in the medullary interstitium. In the base case, the urinary Ca 2ϩ concentration and fractional excretion are predicted as 2.7 mM and 0.32%, respectively. Urinary Ca 2ϩ excretion is found to be strongly modulated by water and NaCl reabsorption along the nephron. Our simulations also suggest that Ca 2ϩ molar flow and concentration profiles differ significantly between superficial and deep nephrons, such that the latter deliver less Ca 2ϩ to the collecting duct. Finally, our results suggest that the DCT and CNT can act to counteract upstream variations in Ca 2ϩ transport but not always sufficiently to prevent hypercalciuria. calcium; finite volume; kidney; mathematical model; transport CALCIUM (CA 2ϩ ) IS THE MOST abundant cation in the body. It plays an essential role in cardiac, skeletal, and smooth muscle function, and extra-and intracellular Ca 2ϩ concentrations ([Ca 2ϩ ]) must therefore be kept within a narrow range. Calcium homeostasis is maintained by the concerted action of the intestine, the parathyroid glands, and the kidneys. Preserving low Ca 2ϩ concentrations in the urinary filtrate is especially important, since hypercalciuria is one of the major risk factors for the formation of kidney stones. Recent studies on Ca 2ϩ handling by the kidney have focused on the molecular transporters and sensors of Ca 2ϩ (2, 9), but our understanding of Ca 2ϩ transport at the organ level remains limited. Whether there is a corticomedullary interstitial [Ca 2ϩ ] gradient has yet to be determined, and the contribution of each nephron segment to perturbations in the renal Ca 2ϩ balance is not fully understood. To address these questions, we developed a mathematical model of renal Ca 2ϩ transport across all nephron segments below the proximal tubules from the descending limbs of Henle to the inner medullary collecting ducts (IMCD). Our model is based on that of Hervy and Thomas (17), referred to below as the HT model, which describes the transport of water, NaCl, glucose, and lactate in the renal medulla. We modified the HT model to 1) make it dynamic, 2) explicitly represent the distal cortical segments, and 3) incorporate Ca 2ϩ transport. For this purpose, we developed a new finite-volume scheme that is robust and fast.About t...

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Section: Calcium Reabsorption In the Talmentioning

confidence: 99%

A model of calcium transport along the rat nephron

Tournus

Seguin

Perthame

et al. 2013

American Journal of Physiology-Renal Physiology

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“…More importantly, the short term effects of vasopressin on TAL electrolyte transport were demonstrated in early studies in isolated microperfused tubules. Addition of vasopressin to the bath stimulates cAMP production (11,12) and transepithelial bumetanide-sensitive chloride fluxes (13)(14)(15)(16). These effects of vasopressin are more pronounced in rodents, whereas they are weak or absent in species with a lesser urinary concentrating ability (17).…”

mentioning

confidence: 99%

Short-term Stimulation of the Renal Na-K-Cl Cotransporter (NKCC2) by Vasopressin Involves Phosphorylation and Membrane Translocation of the Protein

Gíménez

Forbush

2003

Journal of Biological Chemistry

192

218

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Na-K-Cl cotransporter (NKCC2)-mediated sodium chloride reabsorption in the thick ascending limb is stimulated by the antidiuretic hormone vasopressin. We investigate the mechanisms underlying the short term activation of NKCC2 by vasopressin in vivo, finding that administration of a vasopressin analogue (deamino-Cys-D-Arg vasopressin) causes a 2-fold increase in mouse kidney NKCC2 phosphorylation, as detected with a phosphospecific antibody, R5. The subtissue localization of the activation is defined by immunofluorescence. In vasopressin-treated animals, a dramatic increase in R5 immunostaining is observed in the initial segment of the thick ascending limb located in the inner stripe of the outer medulla, the region with a higher sensitivity to vasopressin. Although a pool of NKCC2 is present in cytoplasmic vesicles, the distribution of the phosphorylated cotransporter seems to be restricted to the cell membrane compartment; morphometric analysis of electron microscope images demonstrates a 55% increase in NKCC2 molecules at the apical membrane, suggesting the administration of vasopressin induces trafficking of the cotransporter. Thus, the short term actions of vasopressin on the thick ascending limb cotransporter are mediated by both an effect on the translocation of the protein and an increase in phosphorylation of regulatory threonines in the amino terminus of NKCC2.Vasopressin controls extracellular fluid osmolarity by adjusting the amount of free water excreted by the kidney. The main effect of the hormone is found in the collecting duct, where vasopressin causes insertion of aquaporin channels in the apical membrane (1) and up-regulation of urea transporters (2). However, the amount of water that is finally reabsorbed depends upon the osmolar gradient between the medullary interstitium and the luminal fluid. The existence of a medullary hypertonic interstitium is ensured by the reabsorption of NaCl against its electrochemical gradient in the thick ascending limb of the loop of Henle (TAL).1 Transport of Na ϩ and Cl Ϫ across the luminal membrane of the TAL is provided by the renal isoform of the Na-K-Cl cotransporter, NKCC2, which, in mammals, is exclusively expressed in TAL and macula densa cells (3-5). A rational design of the mechanism responsible for urine concentration would thus include vasopressin stimulation of NKCC2 for the generation of the hypertonic interstitium. The existence of V2-type vasopressin receptors in the TAL strongly supports this hypothesis (6). Several effects of vasopressin on the thick ascending limb Na-K-Cl cotransporter have been reported. NKCC2 protein and messenger RNA levels increased in water deprived rats (7, 8) whereas treatment with a V2-receptor antagonist had the opposite effect (9). In Brattelboro rats, long-term administration of vasopressin restored the function (10) and expression levels of NKCC2 (8), which are significantly reduced in this vasopressin-deficient rat strain. More importantly, the short term effects of vasopressin on TAL electrolyte transport were d...

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“…22 Briefly, the dissected tubules, 0.3 to 0.5 mm in length, were mounted on a set of concentric micropipettes and perfused at 37°C at rates of 2 to 3 nL/min. Asymmetrical conditions of osmolality and sodium concentration for bathing and perfused solutions were chosen 23,18 to maximize water flux and to study precisely both the sodium and water movements.…”

Section: Measurement Of Water and Sodium Transport In Isolated Perfusmentioning

confidence: 99%

Chronic Exposure to Vasopressin Upregulates ENaC and Sodium Transport in the Rat Renal Collecting Duct and Lung

et al. 2001

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Abstract-Vasopressin is known to acutely stimulate sodium transport in the renal collecting duct. We investigated the long-term regulation by vasopressin of the epithelial sodium channel (ENaC) in the rat kidney. Five-day infusion of dDAVP (a V 2 receptor agonist) to Brattleboro rats lacking vasopressin induced a marked increase in ␤-and ␥-subunit ENaC mRNA levels in the renal cortex (␤, 85%; ␥, 100%), with no change in ␣-ENaC mRNA. Expression of ␤-and ␥-ENaC mRNAs was also enhanced in lung (␤, 49%; ␥, 33%) but not in distal colon (an organ devoid of V 2 receptors). Similar results were obtained in Sprague Dawley rats after either partial water restriction or dDAVP infusion for 5 days. Transepithelial voltage and transepithelial sodium and water net fluxes were measured in isolated perfused cortical collecting ducts of Brattleboro rats. Acute addition of 2ϫ10 Ϫ10 mol/L dDAVP to the bath increased sodium and water fluxes in the same proportion, and to a far greater extent in dDAVP-infused than in control Brattleboro rats (change in Na ϩ net flux, 337Ϯ30 versus 49Ϯ11 pmol · min Ϫ1 · mm Ϫ1 , respectively; PϽ0.001). These effects were abolished by amiloride. Extrarenal water losses, partly originating from the lung, were reduced by high plasma vasopressin level. This study shows that vasopressin increases sodium transport in the renal collecting duct and probably in the lung, through a differential transcriptional regulation of ENaC subunits. This effect is followed by isoosmotic water reabsorption and likely contributes to the process of water conservation. It could lead to less efficient sodium excretion, however, and thus participate in some forms of salt-sensitive hypertension.

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Differential effects of ADH on sodium, chloride, potassium, calcium and magnesium transport in cortical and medullary thick ascending limbs of mouse nephron

Cited by 93 publications

References 30 publications

A model of calcium transport along the rat nephron

A model of calcium transport along the rat nephron

Short-term Stimulation of the Renal Na-K-Cl Cotransporter (NKCC2) by Vasopressin Involves Phosphorylation and Membrane Translocation of the Protein

Chronic Exposure to Vasopressin Upregulates ENaC and Sodium Transport in the Rat Renal Collecting Duct and Lung

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