2011 Homer Smith Award

Aperia, Anita

doi:10.1681/asn.2012010102

Cited by 37 publications

(42 citation statements)

References 83 publications

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“…Thus, our data are consistent with the model proposed by Boettger et al (6): that KCC4 in the basolateral membrane of ␣-intercalated cells of the collecting duct could be critical for keeping the intracellular concentration of Cl Ϫ low so that basolateral Cl Ϫ /HCO 3 Ϫ exchanger remains active. This serves to extrude HCO 3 Ϫ from the cell, allowing the continuous production of H ϩ to be secreted in the apical membrane (Fig. 10).…”

Section: Discussionmentioning

confidence: 99%

Molecular evidence for a role for K⁺-Cl⁻ cotransporters in the kidney

Melo

Cruz-Rangel

Bautista

et al. 2013

American Journal of Physiology-Renal Physiology

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K+-Cl− cotransporter (KCC) isoforms 3 (KCC3) and 4 (KCC4) are expressed at the basolateral membrane of proximal convoluted tubule cells, and KCC4 is present in the basolateral membrane of the thick ascending loop of Henle's limb and α-intercalated cells of the collecting duct. Little is known, however, about the physiological roles of these transporters in the kidney. We evaluated KCC3 and KCC4 mRNA and protein expression levels and intrarenal distribution in male Wistar rats or C57 mice under five experimental conditions: hyperglycemia after a single dose of streptozotocin, a low-salt diet, metabolic acidosis induced by ammonium chloride in drinking water, and low- or high-K+ diets. Both KCC3 mRNA and protein expression were increased during hyperglycemia in the renal cortex and at the basolateral membrane of proximal tubule cells but not with a low-salt diet or acidosis. In contrast, KCC4 protein expression was increased by a low-sodium diet in the whole kidney and by metabolic acidosis in the renal outer medulla, specifically at the basolateral membrane of α-intercalated cells. The increased protein expression of KCC4 by a low-salt diet was also observed in WNK4 knockout mice, suggesting that upregulation of KCC4 in these circumstances is not WNK4 dependent. No change in KCC3 or KCC4 protein expression was observed under low- or high-K+ diets. Our data are consistent with a role for KCC3 in the proximal tubule glucose reabsorption mechanism and for KCC4 in salt reabsorption of the thick ascending loop of Henle's loop and acid secretion of the collecting duct.

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Section: Discussionmentioning

confidence: 99%

Molecular evidence for a role for K⁺-Cl⁻ cotransporters in the kidney

Melo

Cruz-Rangel

Bautista

et al. 2013

American Journal of Physiology-Renal Physiology

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“…Direct measurements of solute drag in the proximal tubule of neonates and adults have shown that it contributes a negligible fraction to transport [12][13][14][15]. The Na + /K + -ATPase is located on the basolateral membrane of most tubules in the kidney [16]. It is a heterodimer composed of an a-and b-subunit.…”

Section: Principals Of Membrane Transportmentioning

confidence: 99%

“…At some point, the renal tubular absorption reaches a maximum, called the threshold for that solute, and any further increase in the filtered load is excreted Pediatric Nephrology DOI 10.1007/978-3-642-27843-3_76-1 # Springer-Verlag Berlin Heidelberg 2014 activity [17,[22][23][24][25][26][27][28][29][30][31][32][33][34]. Dopamine and atrial natriuretic factor inhibit, while alpha agonists and angiotensin II stimulate, Na + /K + -ATPase activity [16]. Some hormones such as dopamine have a direct effect to regulate the Na + /K + -ATPase and are independent of an effect on transporters on the apical membrane [22].…”

Section: Principals Of Membrane Transportmentioning

confidence: 99%

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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“…As shown in Fig. 1B, the mechanism responsible for these Ca 2ϩ changes involves the interaction of the N-terminal portions of the Na-KATPase ␣-subunit and the 1,4,5-triphosphate receptor (IP3R) (11). The close proximity between Na-K-ATPase/Src and IP3R constitutes a Ca 2ϩ -signaling microdomain that can transduce the effect of ouabain into endoplasmic reticulum Ca 2ϩ release (125,137,205).…”

Section: Ouabain-na-k-atpase Signalingmentioning

confidence: 99%

Novel role of ouabain as a cystogenic factor in autosomal dominant polycystic kidney disease

Blanco

Wallace

2013

American Journal of Physiology-Renal Physiology

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The classic role of the Na-K-ATPase is that of a primary active transporter that utilizes cell energy to establish and maintain transmembrane Na(+) and K(+) gradients to preserve cell osmotic stability, support cell excitability, and drive secondary active transport. Recent studies have revealed that Na-K-ATPase located within cholesterol-containing lipid rafts serves as a receptor for cardiotonic steroids, including ouabain. Traditionally, ouabain was viewed as a toxin produced only in plants, and it was used in relatively high concentrations to experimentally block the pumping action of the Na-K-ATPase. However, the new and unexpected role of the Na-K-ATPase as a signal transducer revealed a novel facet for ouabain in the regulation of a myriad of cell functions, including cell proliferation, hypertrophy, apoptosis, mobility, and metabolism. The seminal discovery that ouabain is endogenously produced in mammals and circulates in plasma has fueled the interest in this endogenous molecule as a potentially important hormone in normal physiology and disease. In this article, we review the role of the Na-K-ATPase as an ion transporter in the kidney, the experimental evidence for ouabain as a circulating hormone, the function of the Na-K-ATPase as a signal transducer that mediates ouabain's effects, and novel results for ouabain-induced Na-K-ATPase signaling in cystogenesis of autosomal dominant polycystic kidney disease.

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2011 Homer Smith Award

Cited by 37 publications

References 83 publications

Molecular evidence for a role for K⁺-Cl⁻ cotransporters in the kidney

Molecular evidence for a role for K⁺-Cl⁻ cotransporters in the kidney

Renal Tubular Development

Novel role of ouabain as a cystogenic factor in autosomal dominant polycystic kidney disease

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2011 Homer Smith Award

Cited by 37 publications

References 83 publications

Molecular evidence for a role for K+-Cl− cotransporters in the kidney

Molecular evidence for a role for K+-Cl− cotransporters in the kidney

Renal Tubular Development

Novel role of ouabain as a cystogenic factor in autosomal dominant polycystic kidney disease

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Product

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Molecular evidence for a role for K⁺-Cl⁻ cotransporters in the kidney

Molecular evidence for a role for K⁺-Cl⁻ cotransporters in the kidney