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.
Pflugers Arch
2016 May 01;4685:817-24. doi: 10.1007/s00424-016-1794-9.
Show Gene links
Show Anatomy links
The ICl,swell inhibitor DCPIB blocks Kir channels that possess weak affinity for PIP2.
Deng W
,
Mahajan R
,
Baumgarten CM
,
Logothetis DE
.
???displayArticle.abstract???
Inwardly rectifying K(+) (Kir) channels are important contributors to the resting membrane potential and regulate cellular excitability. The activity of Kir channels depends critically on the phospholipid PIP2. Several modulators of the activity of Kir channels alter the apparent affinity of the channel to PIP2. Channels with high apparent affinity to PIP2 may not respond to a given modulator, but mutations that decrease such affinity can render the channel susceptible to modulation. Here, we identify a known inhibitor of the swelling-activated Cl(-) current, DCPIB, as an effective inhibitor of a number of Kir channels both in native cardiac cells and in heterologous expression systems. We show that the apparent affinity to PIP2 determines whether DCPIB will serve as an efficient blocker of Kir channels. These effects are consistent with a model in which DCPIB competes with PIP2 for a common binding site.
Dahlmann,
Regulation of Kir channels by intracellular pH and extracellular K(+): mechanisms of coupling.
2004, Pubmed,
Xenbase
Dahlmann,
Regulation of Kir channels by intracellular pH and extracellular K(+): mechanisms of coupling.
2004,
Pubmed
,
Xenbase
Decher,
DCPIB is a novel selective blocker of I(Cl,swell) and prevents swelling-induced shortening of guinea-pig atrial action potential duration.
2001,
Pubmed
,
Xenbase
Deng,
Endothelin signalling regulates volume-sensitive Cl- current via NADPH oxidase and mitochondrial reactive oxygen species.
2010,
Pubmed
Dobrev,
The G protein-gated potassium current I(K,ACh) is constitutively active in patients with chronic atrial fibrillation.
2005,
Pubmed
Du,
Characteristic interactions with phosphatidylinositol 4,5-bisphosphate determine regulation of kir channels by diverse modulators.
2004,
Pubmed
,
Xenbase
Hibino,
Inwardly rectifying potassium channels: their structure, function, and physiological roles.
2010,
Pubmed
Ho,
Molecular determinants for sodium-dependent activation of G protein-gated K+ channels.
1999,
Pubmed
,
Xenbase
Ichishima,
alpha-Adrenoceptor-mediated depletion of phosphatidylinositol 4, 5-bisphosphate inhibits activation of volume-regulated anion channels in mouse ventricular myocytes.
2010,
Pubmed
Logothetis,
Diverse Kir modulators act in close proximity to residues implicated in phosphoinositide binding.
2007,
Pubmed
Logothetis,
Phosphoinositide-mediated gating of inwardly rectifying K(+) channels.
2007,
Pubmed
Logothetis,
Channelopathies linked to plasma membrane phosphoinositides.
2010,
Pubmed
Logothetis,
Phosphoinositide control of membrane protein function: a frontier led by studies on ion channels.
2015,
Pubmed
Lopes,
PIP2 hydrolysis underlies agonist-induced inhibition and regulates voltage gating of two-pore domain K+ channels.
2005,
Pubmed
,
Xenbase
Lopes,
Protein kinase A modulates PLC-dependent regulation and PIP2-sensitivity of K+ channels.
2007,
Pubmed
,
Xenbase
Mao,
Molecular basis for the inhibition of G protein-coupled inward rectifier K(+) channels by protein kinase C.
2004,
Pubmed
,
Xenbase
Meng,
The molecular mechanism by which PIP(2) opens the intracellular G-loop gate of a Kir3.1 channel.
2012,
Pubmed
Minieri,
The inhibitor of volume-regulated anion channels DCPIB activates TREK potassium channels in cultured astrocytes.
2013,
Pubmed
Nishida,
Crystal structure of a Kir3.1-prokaryotic Kir channel chimera.
2007,
Pubmed
Petit-Jacques,
Synergistic activation of G protein-gated inwardly rectifying potassium channels by the betagamma subunits of G proteins and Na(+) and Mg(2+) ions.
1999,
Pubmed
,
Xenbase
Ponce-Balbuena,
Tamoxifen inhibits inward rectifier K+ 2.x family of inward rectifier channels by interfering with phosphatidylinositol 4,5-bisphosphate-channel interactions.
2009,
Pubmed
Rapedius,
Structural and functional analysis of the putative pH sensor in the Kir1.1 (ROMK) potassium channel.
2006,
Pubmed
,
Xenbase
Rapedius,
Control of pH and PIP2 gating in heteromeric Kir4.1/Kir5.1 channels by H-Bonding at the helix-bundle crossing.
2007,
Pubmed
Rogalski,
TrkB activation by brain-derived neurotrophic factor inhibits the G protein-gated inward rectifier Kir3 by tyrosine phosphorylation of the channel.
2000,
Pubmed
,
Xenbase
Rohács,
Specificity of activation by phosphoinositides determines lipid regulation of Kir channels.
2003,
Pubmed
,
Xenbase
Rosenhouse-Dantsker,
A sodium-mediated structural switch that controls the sensitivity of Kir channels to PtdIns(4,5)P(2).
2008,
Pubmed
Sali,
Comparative protein modelling by satisfaction of spatial restraints.
1993,
Pubmed
Sharman,
IUPHAR-DB: new receptors and tools for easy searching and visualization of pharmacological data.
2011,
Pubmed
Sui,
Activation of the atrial KACh channel by the betagamma subunits of G proteins or intracellular Na+ ions depends on the presence of phosphatidylinositol phosphates.
1998,
Pubmed
,
Xenbase
Sui,
Na+ activation of the muscarinic K+ channel by a G-protein-independent mechanism.
1996,
Pubmed
,
Xenbase
Takano,
Regulation of cardiac inwardly rectifying potassium channels by membrane lipid metabolism.
2003,
Pubmed
Trott,
AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.
2010,
Pubmed
Whorton,
Crystal structure of the mammalian GIRK2 K+ channel and gating regulation by G proteins, PIP2, and sodium.
2011,
Pubmed
,
Xenbase
Xie,
Activation of inwardly rectifying potassium (Kir) channels by phosphatidylinosital-4,5-bisphosphate (PIP2): interaction with other regulatory ligands.
2007,
Pubmed
Yamamoto,
Regulation of volume-regulated outwardly rectifying anion channels by phosphatidylinositol 3,4,5-trisphosphate in mouse ventricular cells.
2008,
Pubmed
Zhang,
Molecular overlap in the regulation of SK channels by small molecules and phosphoinositides.
2015,
Pubmed
Zhang,
Activation of inwardly rectifying K+ channels by distinct PtdIns(4,5)P2 interactions.
1999,
Pubmed
,
Xenbase