Enhancement of electrogenic Na+ transport across rat inner medullary collecting duct by glucocorticoid and by mineralocorticoid hormones.

Husted, Russell F.; Laplace, J R; Stokes, John B.

doi:10.1172/jci114736

Cited by 64 publications

(51 citation statements)

References 56 publications

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“…Using pharmacological inhibitors, we previously showed that MR and GR both contributed to the induction of early aldosterone targets (4). This was consistent with the known contribution of each receptor to aldosterone action (20). To demonstrate hormone receptor-mediated regulation of the Per1 gene, we used an RNA silencing (siRNA) approach to knock down expression of MR, GR, or both receptors.…”

Section: Figuresupporting

confidence: 66%

The circadian clock protein Period 1 regulates expression of the renal epithelial sodium channel in mice

Gumz¹,

Stow²,

Lynch³

et al. 2009

J. Clin. Invest.

190

187

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The mineralocorticoid aldosterone is a major regulator of sodium transport in target epithelia and contributes to the control of blood pressure and cardiac function. It specifically functions to increase renal absorption of sodium from tubular fluid via regulation of the α subunit of the epithelial sodium channel (αENaC). We previously used microarray technology to identify the immediate transcriptional targets of aldosterone in a mouse inner medullary collecting duct cell line and found that the transcript induced to the greatest extent was the circadian clock gene Period 1. Here, we investigated the role of Period 1 in mediating the downstream effects of aldosterone in renal cells. Aldosterone treatment stimulated expression of Period 1 (Per1) mRNA in renal collecting duct cell lines and in the rodent kidney. RNA silencing of Period 1 dramatically decreased expression of mRNA encoding αENaC in the presence or absence of aldosterone. Furthermore, expression of αENaC-encoding mRNA was attenuated in the renal medulla of mice with disruption of the Per1 gene, and these mice exhibited increased urinary sodium excretion. Renal αENaC-encoding mRNA was expressed in an apparent circadian pattern, and this pattern was dramatically altered in mice lacking functional Period genes. These results suggest a role for Period 1 in the regulation of the renal epithelial sodium channel and more broadly implicate the circadian clock in control of sodium balance.

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Section: Figuresupporting

confidence: 66%

The circadian clock protein Period 1 regulates expression of the renal epithelial sodium channel in mice

Gumz¹,

Stow²,

Lynch³

et al. 2009

J. Clin. Invest.

190

187

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“…As the final structure capable of altering the composition of the urine, the renal inner medullary collecting duct (IMCD)1 plays 1. Abbreviations used in this paper: IMCD, inner medullary collecting duct; CCD, cortical collecting duct; ISc, short-circuit current; MC, mineralocorticoid; GC, glucocorticoid; GAPDH, glyceraldehydephosphate dehydrogenase.…”

Section: Introductionmentioning

confidence: 99%

rENaC is the predominant Na+ channel in the apical membrane of the rat renal inner medullary collecting duct.

Volk

Sigmund²,

Snyder³

et al. 1995

J. Clin. Invest.

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The terminal nephron segment, the inner medullary collecting duct (IMCD), absorbs Na+ by an electrogenic process that involves the entry through an apical (luminal) membrane Na+ channel. To understand the nature of this Na+ channel, we employed the patch clamp technique on the apical membrane of primary cultures of rat IMCD cells grown on permeable supports. We found that all ion channels detected in the cell-attached configuration were highly selective for Na+ (Li') over K+. The open/closed transitions showed slow kinetics, had a slope conductance of 6-11 pS, and were sensitive to amiloride and benzamil. Nonselective cation channels with a higher conductance (25-30 pS), known to be present in IMCD cells, were not detected in the cell-attached configuration, but were readily detected in excised patches. The highly selective channels had properties similar to the recently described rat epithelial Na + channel complex, rENaC. We therefore asked whether rENaC mRNA was present in the IMCD. We detected mRNA for all three rENaC subunits in rat renal papilla and also in primary cultures of the IMCD. Either glucocorticoid hormone or mineralocorticoid hormone increased the amount of a-rENaC subunit mRNA but had no effect on the mRNA level of the 8-rENaC or y-rENaC subunits. From these data, taken in the context of other studies on the characteristics of Na+ selective channels and the distribution of rENaC mRNA, we conclude that steroid stimulated Na + absorption by the IMCD is mediated primarily by Na + channels having properties of the rENaC subunit complex. (J. Clin. Invest. 1995. 96:2748-2757

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“…The secretion and absorption of NaCl in IMCD are orchestrated by the actions of various hormones, like aldosterone andor antidiuretic hormone. The mineralocorticoids stimulate electrogenic Na' transport [32] and generate a lumen-negative transepithelial voltage that provides an electrochemical driving force for C1-diffusion across the tight junction [7]. However, antidiuretic hormone (for example during dehydration) increases intracellular CAMP levels 1331 and provides an apical CAMP-stimulated electrogenic C1-secretion [7].…”

mentioning

confidence: 99%

Properties of a Cl⁻‐Conductive Pathway(s) in Microsomes from Rat Kidney Inner Medulla

Benharouoa

Lipecka

Fanen

et al. 1996

European Journal of Biochemistry

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The properties of a protein-kinase-A(PKA)-activated Cl--conductive pathway( s) in alkaline phosphatase-enriched microsomes from the rat inner medulla (IMV) were investigated. Transcripts of cystic fibrosis transmembrane regulator (CFTR) were detected by reverse transcription/polymerase analysis of total RNA from the inner medulla, while immunoblot analysis using anti-CFTR antibodies detected a 170-kDa protein in the IMV. The PKA C1--conductive pathway(s) was studied by measuring the rate of valinomycin-induced microsomal swelling by light scattering. PKA increased the rate of valinomycin-induced swelling of vesicles consistent with the presence of C1--conductive pathway(s). The pharmacological properties and anion selectivity of the PKA-activated Cl--conductive pathway(s) were similar to those of the CFTR CI-channel. Our results show that a CFTR C1 channel and possibly another CAMP-activated pathway(s) may participate in Cl-secretion in the rat inner medulla.Keywords: kidney; inner medulla; cystic fibrosis transmembrane regulator; chloride conductance; chloride channel.The main function of the tubules in the kidney inner medulla, which are mostly collecting ducts (IMCD), is to modify the composition of urine before it leaves the kidney [l], and thus control the concentration of renal excretion. Most functional investigations of IMCD have focused on sodium absorption [2, 31, but recent studies suggest that chloride secretion may also contribute to the regulation of final urine composition and volume [4]. Studies on isolated perfused IMCD from the rat have also shown that CAMP stimulates C1-se.cretion [4-61. It has been suggested that the cystic fibrosis transmembrane regulator (CFTR) chloride channel mediates the electrogenic chloride secretion in mouse IMCD-K2 cells 171 and rat primary cultures of IMCD cells [8]. This is supported by the presence of transcripts for CFTR protein along the nephron [9], and a protein immunologically related to CFTR in the proximal and distal tubules of the human kidney [lo]. To add to the evidence for the presence of a functional CFTR in the IMCD, we performed the present study on microsomes from rat inner medulla (IMV). The goal was to determine whether the CAMP-activated CI-. fluxes in IMV have pharmacological features and anion selectivity similar to those of the CFTR Cl-channel.Reverse transcription, (RT)-PCR, and western blot analysis indicated that CFTR protein is expressed in the inner medulla of the rat kidney. The functional assay based on valinomycininduced vesicle swelling provided evidence that protein-kinase-A (PKA) regulated CI--conductive pathways are present in the inner medulla vesicles (IMV) and that a protein with the pharniacological properties of the CFTR-C1-channel is involved in the regulation of one of these pathways. MATERIALS AND METHODSMaterials. ATP, PKA, valinomycin, phenylmethylsulfonyl fluoride (PhMeSO,F), leupeptin, pepstatin A, Hepes, Tris, 4 acetamido-4'-isothiocyanato-stilbene-2,2'-disulfonic acid, BSA fraction V, and Ponceau S were obtained froin...

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Enhancement of electrogenic Na+ transport across rat inner medullary collecting duct by glucocorticoid and by mineralocorticoid hormones.

Cited by 64 publications

References 56 publications

The circadian clock protein Period 1 regulates expression of the renal epithelial sodium channel in mice

The circadian clock protein Period 1 regulates expression of the renal epithelial sodium channel in mice

rENaC is the predominant Na+ channel in the apical membrane of the rat renal inner medullary collecting duct.

Properties of a Cl⁻‐Conductive Pathway(s) in Microsomes from Rat Kidney Inner Medulla

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Enhancement of electrogenic Na+ transport across rat inner medullary collecting duct by glucocorticoid and by mineralocorticoid hormones.

Cited by 64 publications

References 56 publications

The circadian clock protein Period 1 regulates expression of the renal epithelial sodium channel in mice

The circadian clock protein Period 1 regulates expression of the renal epithelial sodium channel in mice

rENaC is the predominant Na+ channel in the apical membrane of the rat renal inner medullary collecting duct.

Properties of a Cl−‐Conductive Pathway(s) in Microsomes from Rat Kidney Inner Medulla

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Properties of a Cl⁻‐Conductive Pathway(s) in Microsomes from Rat Kidney Inner Medulla