CFTR expression in cortical collecting duct cells

Todd-Turla, Karyn Marie; Rusvai, E.; Náray-Fejes-Tóth, Anikó; Fejes-Tóth, Géza

doi:10.1152/ajprenal.1996.270.1.f237

Cited by 50 publications

(44 citation statements)

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“…With regard to the IKATp-renal sulfonylurea receptor interaction, the absence of the ,-cell sulfonylurea receptor (SUR) from the kidney (14,16) suggests the presence of an alternative sulfonylurea-binding protein. Given the evidence that CFTR is present in kidney (17)(18)(19), it is reasonable to consider that CFTR may play a role as a K+ channel modulator in the mammalian kidney.…”

Section: Discussionmentioning

confidence: 99%

“…This mechanism has been implicated in CFTR regulation of outwardly rectifying chloride channels, which involves the transport of intracellular ATP to the extracellular surface (21 and epithelial sodium channels (27). The sulfonylurea receptor, SUR, (16,19) interacts with IKATP channels and is required for expression of a glibenclamide sensitive K+ conductance. In addition, coexpression of CFTR and epithelial sodium channels effectively inhibit Na+ channel activity in MDCK and 3T3-fibroblast cells (27).…”

Section: Discussionmentioning

confidence: 99%

“…We hypothesized that sulfonylurea sensitivity of renal IKATP may be either conferred to, or enhanced, by a separate channel subunit. (17)(18)(19). CFTR is a cAMP-dependent protein kinase A (PKA)-regulated chloride channel that is sensitive to glibenclamide (20,21).…”

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confidence: 99%

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Sensitivity of a renal K+ channel (ROMK2) to the inhibitory sulfonylurea compound glibenclamide is enhanced by coexpression with the ATP-binding cassette transporter cystic fibrosis transmembrane regulator.

McNicholas

Guggino

Schwiebert

et al. 1996

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

198

124

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We demonstrate here that coexpression of ROMK2, an inwardly rectifying ATP-sensitive renal K+ channel (IKATP) with cystic fibrosis transmembrane regulator (CFTR) significantly enhances the sensitivity of ROMK2 to the sulfonylurea compound glibenclamide. When expressed alone, ROMK2 is relatively insensitive to glibenclamide. The interaction between ROMK2, CFTR, and glibenclamide is modulated by altering the phosphorylation state of either ROMK2, CFTR, or an associated protein, as exogenous MgATP and the catalytic subunit of protein kinase A significantly attenuate the inhibitory effect of glibenclamide on ROMK2. Thus CFIR, which has been demonstrated to interact with both Na+ and Cl-channels in airway epithelium, modulates the function of renal ROMK2 K+ channels.Inwardly rectifying potassium channels occur in a number of excitable and non excitable cells, where they maintain the membrane potential (Em) near the K+ reversal potential (Ek). These channels mediate high K+ conductance at potentials near or slightly positive to EK, but they are decreased when the membrane is depolarized. A defining characteristic of a subgroup of this family, the ATP-sensitive K+ channels (IKATP), is their inhibition by ATP or other nucleotides (1). IKATP channels provide not only a link between the metabolic status of the cell and membrane potential but also a mechanism for K+ secretion in epithelia. ATP-sensitive K+ channels are present in the apical membrane of distal nephron segments of the mammalian kidney where they play a major role in K+ homeostasis (2, 3). IKATp-renal channels share many of the properties and characteristics of other members of this family found in tissues such as heart and pancreas. However, IKATPrenal channels are insensitive to tetraethylammonium chloride, have less sensitivity to ATP (millimolar concentrations are required to induce channel inhibition), and have a lower affinity for sulfonylureas such as glibenclamide than required for inhibition of other IKATP channels. (21,24,25), and epithelial sodium channels (26,27). Using patch clamp techniques, we examined whether CFIR could enhance sulfonylurea sensitivity of ROMK2. We coexpressed both CFTR and ROMK2 cRNA in Xenopus oocytes and assayed for glibenclamide sensitivity. We now present evidence that demonstrates that CFTR enhances sulfonylurea sensitivity of ROMK2, and that the interaction between these two proteins is modulated by phosphorylation.Preliminary reports of these data have been presented in abstract form (28,29). MATERIALS AND METHODSPreparation ofXenopus Oocytes for cRNA Expression. Stage V-VI oocytes were isolated by partial ovariectomy under tricaine anesthesia. Oocytes were then defolliculated by treatment with 2 mg of collagenase per ml (Boehringer Mannheim) in Ca2+-free hypotonic solution (82.5 mM NaCl/2.0 mM KC1/1.8 mM MgCl2/5.0 mM Hepes, pH 7.4). Oocytes were Abbreviations: ABC, ATP-binding cassette; CFTR, cystic fibrosis transmembrane regulator; PKA, protein kinase A. §To whom reprint requests should be addressed at:

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Sensitivity of a renal K+ channel (ROMK2) to the inhibitory sulfonylurea compound glibenclamide is enhanced by coexpression with the ATP-binding cassette transporter cystic fibrosis transmembrane regulator.

McNicholas

Guggino

Schwiebert

et al. 1996

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

198

124

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“…3C). They also expressed mRNAs for TLR2 and for the ENaC ␣-subunit and CFTR Cl Ϫ channel, both of which were expressed in principal and intercalated cells (39,40) (Fig. 3C).…”

Section: Pyelonephritic E Coli Strains Interact With Renal Collectinmentioning

confidence: 99%

Renal Collecting Duct Epithelial Cells React to Pyelonephritis-Associated Escherichia coli by Activating Distinct TLR4-Dependent and -Independent Inflammatory Pathways

Chassin

Goujon

Darche³

et al. 2006

The Journal of Immunology

119

156

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TLR4 plays a central role in resistance to pyelonephritis caused by uropathogenic Escherichia coli (UPEC). It has been suggested that renal tubule epithelial cells expressing TLRs may play a key role in inflammatory disorders and in initiating host defenses. In this study we used an experimental mouse model of ascending urinary tract infection to show that UPEC isolates preferentially adhered to the apical surface of medullary collecting duct (MCD) intercalated cells. UPEC-infected C3H/HeJ (Lpsd) mice carrying an inactivating mutation of tlr4 failed to clear renal bacteria and exhibited a dramatic slump in proinflammatory mediators as compared with infected wild-type C3H/HeOuJ (Lpsn) mice. However, the level of expression of the leukocyte chemoattractants MIP-2 and TNF-α still remained greater in UPEC-infected than in naive C3H/HeJ (Lpsd) mice. Using primary cultures of microdissected Lpsn MCDs that expressed TLR4 and its accessory molecules MD2, MyD88, and CD14, we also show that UPECs stimulated both a TLR4-mediated, MyD88-dependent, TIR domain-containing adaptor-inducing IFN-β-independent pathway and a TLR4-independent pathway, leading to bipolarized secretion of MIP-2. Stimulation by UPECs of the TLR4-mediated pathway in Lpsn MCDs leads to the activation of NF-κB, and MAPK p38, ERK1/2, and JNK. In addition, UPECs stimulated TLR4-independent signaling by activating a TNF receptor-associated factor 2-apoptosis signal-regulatory kinase 1-JNK pathway. These findings demonstrate that epithelial collecting duct cells are actively involved in the initiation of an immune response via several distinct signaling pathways and suggest that intercalated cells play an active role in the recognition of UPECs colonizing the kidneys.

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“…There are multiple different pathways involved in the transport of solutes across the cell plasma membrane. Ion transport across principal cells is mediated by sodium (Duc et al 1994;Bachmann et al 1999;Loffing and Kaissling 2003;Frindt et al 2007), potassium (Frindt and Palmer 1987;Frindt and Palmer 1989;Muto 2001;Najjar et al 2005) and chloride (Sansom et al 1990;Todd-Turla et al 1996) channels, Na/K-pumps (Feraille and Doucet 2001;Wetzel and Sweadner 2001) and several types of ion transporters (Kuwahara et al 1991;Chou et al 2008). It is thus important to quantify the relative contribution of the various transporting mechanisms to the net transmembrane ion flux in order to understand the mechanism of the maintenance of the water-electrolyte balance in a principal cell.…”

Section: Introductionmentioning

confidence: 99%

Quantitative estimation of transmembrane ion transport in rat renal collecting duct principal cells

Ilyaskin

Karpov²,

Медведев³

et al. 2014

gpb

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Abstract. Kidney collecting duct principal cells play a key role in regulated tubular reabsorption of water and sodium and secretion of potassium. The importance of this function for the maintenance of the osmotic homeostasis of the whole organism motivates extensive study of the ion transport properties of collecting duct principal cells.We performed experimental measurements of cell volume and intracellular sodium concentration in rat renal collecting duct principal cells from the outer medulla (OMCD) and used a mathematical model describing transmembrane ion fluxes to analyze the experimental data. The sodium and chloride concentrations ([Na + ] in = 37.3 ± 3.3 mM, [Cl -] in = 32.2 ± 4.0 mM) in OMCD cells were quantitatively estimated. Correspondence between the experimentally measured cell physiological characteristics and the values of model permeability parameters was established. Plasma membrane permeabilities and the rates of transmembrane fluxes for sodium, potassium and chloride ions were estimated on the basis of ion substitution experiments and model predictions. In particular, calculated sodium (P Na ), potassium (P K ) and chloride (P Cl ) permeabilities were equal to 3.2 × 10 -6 cm/s, 1.0 × 10 -5 cm/s and 3.0 × 10 -6 cm/s, respectively. This approach sets grounds for utilization of experimental measurements of intracellular sodium concentration and cell volume to quantify the ion permeabilities of OMCD principal cells and aids us in understanding the physiology of the adjustment of renal sodium and potassium excretion.

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CFTR expression in cortical collecting duct cells

Cited by 50 publications

References 0 publications

Sensitivity of a renal K+ channel (ROMK2) to the inhibitory sulfonylurea compound glibenclamide is enhanced by coexpression with the ATP-binding cassette transporter cystic fibrosis transmembrane regulator.

Sensitivity of a renal K+ channel (ROMK2) to the inhibitory sulfonylurea compound glibenclamide is enhanced by coexpression with the ATP-binding cassette transporter cystic fibrosis transmembrane regulator.

Renal Collecting Duct Epithelial Cells React to Pyelonephritis-Associated Escherichia coli by Activating Distinct TLR4-Dependent and -Independent Inflammatory Pathways

Quantitative estimation of transmembrane ion transport in rat renal collecting duct principal cells

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