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.
???displayArticle.abstract???
The pH-sensitive renal potassium channel Kir1.1 is important for K+ homeostasis. Disruption of the pH-sensing mechanism causes type II Bartter syndrome. The pH sensor is thought to be an anomalously titrated lysine residue (K80) that interacts with two arginine residues as part of an 'RKR triad'. We show that a Kir1.1 orthologue from Fugu rubripes lacks this lysine and yet is still highly pH sensitive, indicating that K80 is not the H+ sensor. Instead, K80 functionally interacts with A177 on transmembrane domain 2 at the 'helix-bundle crossing' and controls the ability of pH-dependent conformational changes to induce pore closure. Although not required for pH inhibition, K80 is indispensable for the coupling of pH gating to the extracellular K+ concentration, explaining its conservation in most Kir1.1 orthologues. Furthermore, we demonstrate that instead of interacting with K80, the RKR arginine residues form highly conserved inter- and intra-subunit interactions that are important for Kir channel gating and influence pH sensitivity indirectly.
Antcliff,
Functional analysis of a structural model of the ATP-binding site of the KATP channel Kir6.2 subunit.
2005, Pubmed
Antcliff,
Functional analysis of a structural model of the ATP-binding site of the KATP channel Kir6.2 subunit.
2005,
Pubmed Ashcroft,
ATP-sensitive potassium channelopathies: focus on insulin secretion.
2005,
Pubmed Dahlmann,
Regulation of Kir channels by intracellular pH and extracellular K(+): mechanisms of coupling.
2004,
Pubmed
,
Xenbase Fakler,
Identification of a titratable lysine residue that determines sensitivity of kidney potassium channels (ROMK) to intracellular pH.
1996,
Pubmed
,
Xenbase Hebert,
Bartter syndrome.
2003,
Pubmed Hebert,
Molecular diversity and regulation of renal potassium channels.
2005,
Pubmed Kuo,
Crystal structure of the potassium channel KirBac1.1 in the closed state.
2003,
Pubmed Lopes,
Alterations in conserved Kir channel-PIP2 interactions underlie channelopathies.
2002,
Pubmed
,
Xenbase Nishida,
Structural basis of inward rectification: cytoplasmic pore of the G protein-gated inward rectifier GIRK1 at 1.8 A resolution.
2002,
Pubmed Pegan,
Cytoplasmic domain structures of Kir2.1 and Kir3.1 show sites for modulating gating and rectification.
2005,
Pubmed
,
Xenbase Peters,
Classification and rescue of ROMK mutations underlying hyperprostaglandin E syndrome/antenatal Bartter syndrome.
2003,
Pubmed
,
Xenbase Sackin,
Structural locus of the pH gate in the Kir1.1 inward rectifier channel.
2005,
Pubmed
,
Xenbase Schulte,
Gating of inward-rectifier K+ channels by intracellular pH.
2000,
Pubmed
,
Xenbase Schulte,
K(+)-dependent gating of K(ir)1.1 channels is linked to pH gating through a conformational change in the pore.
2001,
Pubmed
,
Xenbase Schulte,
pH-dependent gating of ROMK (Kir1.1) channels involves conformational changes in both N and C termini.
1998,
Pubmed
,
Xenbase Schulte,
pH gating of ROMK (K(ir)1.1) channels: control by an Arg-Lys-Arg triad disrupted in antenatal Bartter syndrome.
1999,
Pubmed Trapp,
Molecular analysis of ATP-sensitive K channel gating and implications for channel inhibition by ATP.
1998,
Pubmed
,
Xenbase Vize,
A Homeric view of kidney evolution: A reprint of H.W. Smith's classic essay with a new introduction. Evolution of the kidney. 1943.
2004,
Pubmed
,
Xenbase Wang,
Determinant role of membrane helices in K ATP channel gating.
2005,
Pubmed
,
Xenbase Yi,
Yeast screen for constitutively active mutant G protein-activated potassium channels.
2001,
Pubmed
,
Xenbase
