Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Am J Physiol Cell Physiol
2013 Mar 01;3045:C440-9. doi: 10.1152/ajpcell.00363.2012.
Show Gene links
Show Anatomy links
Characterization of the R162W Kir7.1 mutation associated with snowflake vitreoretinopathy.
Zhang W
,
Zhang X
,
Wang H
,
Sharma AK
,
Edwards AO
,
Hughes BA
.
???displayArticle.abstract??? KCNJ13 encodes Kir7.1, an inwardly rectifying K(+) channel that is expressed in multiple ion-transporting epithelia. A mutation in KCNJ13 resulting in an arginine-to-tryptophan change at residue 162 (R162W) of Kir7.1 was associated with snowflake vitreoretinal degeneration, an inherited autosomal-dominant disease characterized by vitreous degeneration and mild retinal degeneration. We used the Xenopus laevis oocyte expression system to assess the functional properties of the R162W (mutant) Kir7.1 channel and determine how wild-type (WT) Kir7.1 is affected by the presence of the mutant subunit. Recordings obtained via the two-electrode voltage-clamp technique revealed that injection of oocytes with mutant Kir7.1 cRNA resulted in currents and cation selectivity that were indistinguishable from those in water-injected oocytes, suggesting that the mutant protein does not form functional channels in the plasma membrane. Coinjection of oocytes with equal amounts of mutant and WT Kir7.1 cRNAs resulted in inward K(+) and Rb(+) currents with amplitudes that were ∼17% of those in oocytes injected with WT Kir7.1 cRNA alone, demonstrating a dominant-negative effect of the mutant subunit. Similar to oocytes injected with WT Kir7.1 cRNA alone, coinjected oocytes exhibited inwardly rectifying Rb(+) currents that were more than seven times larger than K(+) currents, indicating that mutant subunits did not alter Kir7.1 channel selectivity. Immunostaining of Xenopus oocytes or Madin-Darby canine kidney cells expressing mutant or WT Kir7.1 demonstrated distribution of both proteins primarily in the plasma membrane. Our data suggest that the R162W mutation suppresses Kir7.1 channel activity, possibly by negatively impacting gating by membrane phosphadidylinositol 4,5-bisphosphate.
Bialek,
K+ and Cl- transport mechanisms in bovine pigment epithelium that could modulate subretinal space volume and composition.
1994, Pubmed
Bialek,
K+ and Cl- transport mechanisms in bovine pigment epithelium that could modulate subretinal space volume and composition.
1994,
Pubmed
Denning,
Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive.
1992,
Pubmed
,
Xenbase
Derst,
Cellular localization of the potassium channel Kir7.1 in guinea pig and human kidney.
2001,
Pubmed
,
Xenbase
Döring,
The epithelial inward rectifier channel Kir7.1 displays unusual K+ permeation properties.
1998,
Pubmed
,
Xenbase
Edelman,
Epinephrine stimulates fluid absorption across bovine retinal pigment epithelium.
1991,
Pubmed
Flagg,
A mutation linked with Bartter's syndrome locks Kir 1.1a (ROMK1) channels in a closed state.
1999,
Pubmed
,
Xenbase
Hansen,
Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2.
2011,
Pubmed
Hejtmancik,
Mutations in KCNJ13 cause autosomal-dominant snowflake vitreoretinal degeneration.
2008,
Pubmed
Hirose,
Snowflake degeneration in hereditary vitreoretinal degeneration.
1974,
Pubmed
Huang,
Light-evoked expansion of subretinal space volume in the retina of the frog.
1992,
Pubmed
Hughes,
Effects of Ba2+ and Cs+ on apical membrane K+ conductance in toad retinal pigment epithelium.
1995,
Pubmed
Joseph,
Apical and basal membrane ion transport mechanisms in bovine retinal pigment epithelium.
1991,
Pubmed
Krapivinsky,
A novel inward rectifier K+ channel with unique pore properties.
1998,
Pubmed
Kusaka,
Functional Kir7.1 channels localized at the root of apical processes in rat retinal pigment epithelium.
2001,
Pubmed
Li,
Light-dependent hydration of the space surrounding photoreceptors in chick retina.
1994,
Pubmed
Lopes,
Alterations in conserved Kir channel-PIP2 interactions underlie channelopathies.
2002,
Pubmed
,
Xenbase
MacKinnon,
Determination of the subunit stoichiometry of a voltage-activated potassium channel.
1991,
Pubmed
,
Xenbase
Miller,
Active ion transport pathways in the bovine retinal pigment epithelium.
1990,
Pubmed
Nakamura,
Inwardly rectifying K+ channel Kir7.1 is highly expressed in thyroid follicular cells, intestinal epithelial cells and choroid plexus epithelial cells: implication for a functional coupling with Na+,K+-ATPase.
1999,
Pubmed
Ookata,
Localization of inward rectifier potassium channel Kir7.1 in the basolateral membrane of distal nephron and collecting duct.
2000,
Pubmed
Pattnaik,
Genetic defects in the hotspot of inwardly rectifying K(+) (Kir) channels and their metabolic consequences: a review.
2012,
Pubmed
Peterson,
Extracellular ATP activates calcium signaling, ion, and fluid transport in retinal pigment epithelium.
1997,
Pubmed
Sergouniotis,
Recessive mutations in KCNJ13, encoding an inwardly rectifying potassium channel subunit, cause leber congenital amaurosis.
2011,
Pubmed
Shimura,
Expression and permeation properties of the K(+) channel Kir7.1 in the retinal pigment epithelium.
2001,
Pubmed
,
Xenbase
Steinberg,
Three light-evoked responses of the retinal pigment epithelium.
1983,
Pubmed
Strauss,
The retinal pigment epithelium in visual function.
2005,
Pubmed
Tateno,
Role of C-terminus of Kir7.1 potassium channel in cell-surface expression.
2006,
Pubmed
Wischmeyer,
Stable cation coordination at a single outer pore residue defines permeation properties in Kir channels.
2000,
Pubmed
,
Xenbase
Yang,
Expression and localization of the inwardly rectifying potassium channel Kir7.1 in native bovine retinal pigment epithelium.
2003,
Pubmed
Yasuda,
Expression and functional properties of unique inward rectifier K+ channel Kir7.1 in the porcine iris and retinal pigment epithelium.
2003,
Pubmed
la Cour,
Potassium transport of the frog retinal pigment epithelium: autoregulation of potassium activity in the subretinal space.
1986,
Pubmed