Primary structure and functional properties of an epithelial K channel

Zhou, Hao; Tate, Suresh S.; Palmer, Lawrence G.

doi:10.1152/ajpcell.1994.266.3.c809

Cited by 161 publications

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“…However, a small though appreciable decline of channel activity occurs at lower concentrations of glibenclamide. This apparent sensitivity could be mediated by two separate effects: (i) Mg2+-independent channel rundown (32) and (ii) the expression of an endogenous peptide that serves as a sulfonylurea receptor (9). Previous voltage clamp studies demonstrated that application of glibenclamide produced an inconsistent effect on K+ currents inXenopus oocytes injected with ROMK2 cRNA (9).…”

Section: Resultsmentioning

confidence: 99%

“…Recently several inwardly rectifying potassium channels, which contain two transmembrane spanning domains characteristic of this rapidly expanding family of K+ channels, have been cloned (5)(6)(7)(8)(9)(10)(11)(12)(13)(14). A potassium channel of renal origin (ROMK2), an alternative splice isoform of ROMK1 cloned from the outer medulla of the rat kidney (5,9,10), is an ATP-sensitive K+ channel (15).…”

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confidence: 99%

“…A potassium channel of renal origin (ROMK2), an alternative splice isoform of ROMK1 cloned from the outer medulla of the rat kidney (5,9,10), is an ATP-sensitive K+ channel (15). While ROMK2 shares many characteristics with "native" IKATp-renal, ROMK2 exhibits only low and highly variable sensitivity to sulfonylurea compounds, such as glibenclamide (9). We hypothesized that sulfonylurea sensitivity of renal IKATP may be either conferred to, or enhanced, by a separate channel subunit.…”

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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: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…This understanding has been fueled by the molecular identification of Na-K-2Cl cotransporter (NKCC2) (5,6), K ϩ secretory channel (ROMK) (7,8), and basolateral Cl Ϫ channel (ClC-K2) (9)(10)(11)(12) expressed in the TALH of mammalian kidney.…”

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confidence: 99%

Kidney-specific chloride channel, OmClC-K, predominantly expressed in the diluting segment of freshwater-adapted tilapia kidney

Mitsuya

Kaneko²,

Uchida³

et al. 2002

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

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The kidney plays an important role in osmoregulation in freshwater teleosts, which are exposed to the danger of osmotic loss of Na ؉ and Cl ؊ . However, ion-transport mechanisms in the kidney are poorly understood, and ion transporters of the fish nephron have not been identified thus far. From Mozambique tilapia, Oreochromis mossambicus, we have cloned a chloride channel, which is a homologue of the mammalian kidney-specific chloride channel, ClC-K. The cDNA of the channel, named OmClC-K, encodes a protein whose amino acid sequence has high homology to Xenopus and mammalian ClC-K (Xenopus ClC-K, 41.8%; rat ClC-K2, 40.9%; rat ClC-K1, 40.1%). The mRNA of OmClC-K was expressed exclusively in the kidney, and the expression level of mRNA was increased more in freshwater-adapted fish than seawater-adapted fish. The immunohistochemical study using a specific antibody showed that OmClC-K-positive cells were specifically located in the distal nephron segments. Immunoelectron microscopy further showed that immunoreaction of OmClC-K was recognizable on the structure of basolateral membrane infoldings in the distal tubule cells. The localization of OmClC-K and its induction in hypoosmotic media suggest that OmClC-K is involved in Cl ؊ reabsorption in the distal tubule of freshwater-adapted tilapia.T he kidney plays an important role in osmoregulation in both freshwater and seawater teleosts, although its function is entirely different under the two different environmental conditions. Freshwater teleosts are exposed to the danger of osmotic water load and ion loss. Accordingly, the primary function of their kidneys is to excrete excess water, while reabsorbing most of the filtered solutes. The glomerular filtration rate of freshwater teleosts is higher than that of marine teleosts, and sometimes as much as 95% of the filtered water is excreted as copious dilute urine, which implies that the renal tubules of freshwater teleosts must generally have low water permeability. The nephron of freshwater teleosts is composed of a well-developed glomerulus, a ciliated neck segment, a proximal tubule, an intermediate segment, a distal tubule, and a collecting tubule, but it lacks the loop of Henle (1). The teleost kidney exhibits neither zonation, such as the cortex and medulla, nor a countercurrent system of tubular elements. Thus, teleosts are not able to excrete hyperosmotic urine.Nishimura et al. (2) measured water and ion transport in nephron tubules isolated from freshwater-adapted rainbow trout, Oncorhynchus mykiss. They perfused nephron tubules and measured water and ion transport in the distal tubule. These results suggest that in freshwater-adapted rainbow trout, the distal tubule acts as a diluting segment, which is equivalent to the early distal segment of the frog kidney and the mammalian thick ascending limb of Henle's loop (TALH) (3, 4).The extraction of NaCl from urine in the TALH is crucial to urinary concentration and dilution, which is accomplished by the active reabsorption of NaCl in the water-impermeable epitheli...

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“…Although the recombinant ROMK channel, as expressed in Xenopus oocytes, has been reported to by some investigators to exhibit sensitivity to the sulfonylurea K ATP channel blocker glibenclamide (43), we and others (44) have found that the response is modest, highly variable, and dependent on oocyte donor, suggesting the involvement of inconsistently expressed factors in the oocyte (44). Consequently, to study the effects of CFTR and NHERF on ROMK in the present study, we used a stock of frogs that was prescreened for lack of glibenclamide effects on expressed ROMK.…”

Section: Methodsmentioning

confidence: 76%

Assembly and Trafficking of a Multiprotein ROMK (Kir 1.1) Channel Complex by PDZ Interactions

Yoo

Flagg

Olsen

et al. 2004

Journal of Biological Chemistry

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The ROMK subtypes of inward rectifier K ؉ channels (Kir 1.1, KCNJ1) mediate potassium secretion and regulate NaCl reabsorption in the kidney. In the present study, the role of the PDZ binding motif in ROMK function is explored. Here we identify the Na/H exchange regulatory factors, NHERF-1 and NHERF-2, as PDZ domain interaction partners of the ROMK channel. Characterization of the basis and consequences of NHERF association with ROMK reveals a PDZ interaction-dependent trafficking process and a coupling mechanism for linking ROMK to a channel modifier protein, the cystic fibrosis transmembrane regulator (CFTR). As

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Primary structure and functional properties of an epithelial K channel

Cited by 161 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.

Kidney-specific chloride channel, OmClC-K, predominantly expressed in the diluting segment of freshwater-adapted tilapia kidney

Assembly and Trafficking of a Multiprotein ROMK (Kir 1.1) Channel Complex by PDZ Interactions

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