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J Clin Invest
2006 Mar 01;1163:797-807. doi: 10.1172/JCI26961.
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CFTR is required for PKA-regulated ATP sensitivity of Kir1.1 potassium channels in mouse kidney.
Lu M, Leng Q, Egan ME, Caplan MJ, Boulpaep EL, Giebisch GH, Hebert SC.
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The cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel plays vital roles in fluid transport in many epithelia. While CFTR is expressed along the entire nephron, its function in renal tubule epithelial cells remains unclear, as no specific renal phenotype has been identified in cystic fibrosis. CFTR has been proposed as a regulator of the 30 pS, ATP-sensitive renal K channel (Kir1.1, also known as renal outer medullar K [ROMK]) that is critical for K secretion by cells of the thick ascending limb (TAL) and distalnephron segments responsive to aldosterone. We report here that both ATP and glibenclamide sensitivities of the 30 pS K channel in TAL cells were absent in mice lacking CFTR and in mice homozygous for the deltaF508 mutation. Curcumin treatment in deltaF508-CFTR mice partially reversed the defect in ATP sensitivity. We demonstrate that the effect of CFTR on ATP sensitivity was abrogated by increasing PKA activity. We propose that CFTR regulates the renal K secretory channel by providing a PKA-regulated functional switch that determines the distribution of open and ATP-inhibited K channels in apical membranes. We discuss the potential physiological role of this functional switch in renal K handling during water diuresis and the relevance to renal K homeostasis in cystic fibrosis.
Aguilar-Bryan,
Toward understanding the assembly and structure of KATP channels.
1998, Pubmed
Aguilar-Bryan,
Toward understanding the assembly and structure of KATP channels.
1998,
Pubmed Bates,
Cystic fibrosis presenting with hypokalemia and metabolic alkalosis in a previously healthy adolescent.
1997,
Pubmed Berger,
Identification and regulation of the cystic fibrosis transmembrane conductance regulator-generated chloride channel.
1991,
Pubmed Berger,
Curcumin stimulates cystic fibrosis transmembrane conductance regulator Cl- channel activity.
2005,
Pubmed Cahill,
Identification of the cystic fibrosis transmembrane conductance regulator domains that are important for interactions with ROMK2.
2000,
Pubmed
,
Xenbase Cassola,
Vasopressin increases density of apical low-conductance K+ channels in rat CCD.
1993,
Pubmed Crawford,
Immunocytochemical localization of the cystic fibrosis gene product CFTR.
1991,
Pubmed Devidas,
The cystic fibrosis transmembrane conductance regulator and ATP.
1997,
Pubmed Devuyst,
Chloride channels in the kidney: lessons learned from knockout animals.
2002,
Pubmed Devuyst,
Developmental regulation of CFTR expression during human nephrogenesis.
1996,
Pubmed Dong,
Novel nucleotide-binding sites in ATP-sensitive potassium channels formed at gating interfaces.
2005,
Pubmed
,
Xenbase Dragomir,
Curcumin does not stimulate cAMP-mediated chloride transport in cystic fibrosis airway epithelial cells.
2004,
Pubmed Dransfield,
Ezrin is a cyclic AMP-dependent protein kinase anchoring protein.
1997,
Pubmed Egan,
Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects.
2004,
Pubmed Egan,
CFTR-associated ATP transport and release.
2002,
Pubmed Field,
Influence of ADH on renal potassium handling: a micropuncture and microperfusion study.
1984,
Pubmed Gadsby,
Control of CFTR channel gating by phosphorylation and nucleotide hydrolysis.
1999,
Pubmed Grubb,
Intestinal physiology and pathology in gene-targeted mouse models of cystic fibrosis.
1997,
Pubmed Hebert,
Effects of antidiuretic hormone on cellular conductive pathways in mouse medullary thick ascending limbs of Henle: I. ADH increases transcellular conductance pathways.
1984,
Pubmed Hebert,
Hypertonic cell volume regulation in mouse thick limbs. II. Na+-H+ and Cl(-)-HCO3- exchange in basolateral membranes.
1986,
Pubmed Hebert,
Molecular diversity and regulation of renal potassium channels.
2005,
Pubmed Ho,
Cloning and expression of an inwardly rectifying ATP-regulated potassium channel.
1993,
Pubmed
,
Xenbase Holland,
Metabolic alkalosis contributes to acute hypercapnic respiratory failure in adult cystic fibrosis.
2003,
Pubmed Huang,
Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma.
1998,
Pubmed
,
Xenbase Inagaki,
Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor.
1995,
Pubmed Kunzelmann,
CFTR: interacting with everything?
2001,
Pubmed Ladias,
Structural insights into the CFTR-NHERF interaction.
2003,
Pubmed Li,
Molecular assembly of cystic fibrosis transmembrane conductance regulator in plasma membrane.
2004,
Pubmed Liou,
Regulation of ROMK1 channel by protein kinase A via a phosphatidylinositol 4,5-bisphosphate-dependent mechanism.
1999,
Pubmed
,
Xenbase Loo,
Thapsigargin or curcumin does not promote maturation of processing mutants of the ABC transporters, CFTR, and P-glycoprotein.
2004,
Pubmed Lorenz,
Impaired renal NaCl absorption in mice lacking the ROMK potassium channel, a model for type II Bartter's syndrome.
2002,
Pubmed Lu,
Extracellular ATP inhibits the small-conductance K channel on the apical membrane of the cortical collecting duct from mouse kidney.
2000,
Pubmed Lu,
ROMK is required for expression of the 70-pS K channel in the thick ascending limb.
2004,
Pubmed Lu,
Hydrolyzable ATP and PIP(2) modulate the small-conductance K+ channel in apical membranes of rat cortical-collecting duct (CCD).
2002,
Pubmed
,
Xenbase Lu,
Absence of small conductance K+ channel (SK) activity in apical membranes of thick ascending limb and cortical collecting duct in ROMK (Bartter's) knockout mice.
2002,
Pubmed MacGregor,
Partially active channels produced by PKA site mutation of the cloned renal K+ channel, ROMK2 (kir1.2).
1998,
Pubmed
,
Xenbase Mall,
Correction of the CF defect by curcumin: hypes and disappointments.
2005,
Pubmed McNicholas,
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.
1996,
Pubmed
,
Xenbase McNicholas,
pH-dependent modulation of the cloned renal K+ channel, ROMK.
1998,
Pubmed
,
Xenbase McNicholas,
A functional CFTR-NBF1 is required for ROMK2-CFTR interaction.
1997,
Pubmed
,
Xenbase McNicholas,
Molecular site for nucleotide binding on an ATP-sensitive renal K+ channel (ROMK2).
1996,
Pubmed
,
Xenbase Morales,
Both the wild type and a functional isoform of CFTR are expressed in kidney.
1996,
Pubmed
,
Xenbase NULL,
Mutations in the gene encoding the inwardly-rectifying renal potassium channel, ROMK, cause the antenatal variant of Bartter syndrome: evidence for genetic heterogeneity. International Collaborative Study Group for Bartter-like Syndromes.
1997,
Pubmed O'Connell,
Phosphorylation-regulated endoplasmic reticulum retention signal in the renal outer-medullary K+ channel (ROMK).
2005,
Pubmed
,
Xenbase Raghuram,
Regulation of cystic fibrosis transmembrane conductance regulator single-channel gating by bivalent PDZ-domain-mediated interaction.
2001,
Pubmed Reisin,
The cystic fibrosis transmembrane conductance regulator is a dual ATP and chloride channel.
1994,
Pubmed Riordan,
Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.
1989,
Pubmed Ruknudin,
Novel subunit composition of a renal epithelial KATP channel.
1998,
Pubmed
,
Xenbase Schafer,
Vasopressin and mineralocorticoid increase apical membrane driving force for K+ secretion in rat CCD.
1990,
Pubmed Schafer,
Effect of ADH on rubidium transport in isolated perfused rat cortical collecting tubules.
1986,
Pubmed Schwiebert,
CFTR is a conductance regulator as well as a chloride channel.
1999,
Pubmed Sheppard,
Structure and function of the CFTR chloride channel.
1999,
Pubmed Simon,
Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K+ channel, ROMK.
1996,
Pubmed Song,
Evidence against the rescue of defective DeltaF508-CFTR cellular processing by curcumin in cell culture and mouse models.
2004,
Pubmed Stanton,
Cystic fibrosis transmembrane conductance regulator (CFTR) and renal function.
1997,
Pubmed Sun,
E3KARP mediates the association of ezrin and protein kinase A with the cystic fibrosis transmembrane conductance regulator in airway cells.
2000,
Pubmed
,
Xenbase Tabcharani,
Phosphorylation-regulated Cl- channel in CHO cells stably expressing the cystic fibrosis gene.
1991,
Pubmed Tanemoto,
Rat homolog of sulfonylurea receptor 2B determines glibenclamide sensitivity of ROMK2 in Xenopus laevis oocyte.
2000,
Pubmed
,
Xenbase Tucker,
Molecular determinants of KATP channel inhibition by ATP.
1998,
Pubmed
,
Xenbase Tucker,
A touching case of channel regulation: the ATP-sensitive K+ channel.
1998,
Pubmed Unwin,
Purinergic signaling along the renal tubule: the current state of play.
2003,
Pubmed Vanoye,
The carboxyl termini of K(ATP) channels bind nucleotides.
2002,
Pubmed Wang,
Activating cystic fibrosis transmembrane conductance regulator channels with pore blocker analogs.
2005,
Pubmed Wang,
Dual effect of adenosine triphosphate on the apical small conductance K+ channel of the rat cortical collecting duct.
1991,
Pubmed Wang,
A potassium channel in the apical membrane of rabbit thick ascending limb of Henle's loop.
1990,
Pubmed Wang,
Effects of glyburide on renal tubule transport and potassium-channel activity.
1995,
Pubmed Xu,
Phosphorylation of the ATP-sensitive, inwardly rectifying K+ channel, ROMK, by cyclic AMP-dependent protein kinase.
1996,
Pubmed
,
Xenbase Yoo,
Assembly and trafficking of a multiprotein ROMK (Kir 1.1) channel complex by PDZ interactions.
2004,
Pubmed
,
Xenbase Zeiher,
A mouse model for the delta F508 allele of cystic fibrosis.
1995,
Pubmed Zerangue,
A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels.
1999,
Pubmed
,
Xenbase Zhou,
Correction of lethal intestinal defect in a mouse model of cystic fibrosis by human CFTR.
1994,
Pubmed
