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.
J Biol Chem
2018 Mar 09;29310:3546-3561. doi: 10.1074/jbc.RA117.001679.
Show Gene links
Show Anatomy links
Hydrogen sulfide inhibits Kir2 and Kir3 channels by decreasing sensitivity to the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2).
Ha J, Xu Y, Kawano T, Hendon T, Baki L, Garai S, Papapetropoulos A, Thakur GA, Plant LD, Logothetis DE.
???displayArticle.abstract???
Inwardly rectifying potassium (Kir) channels establish and regulate the resting membrane potential of excitable cells in the heart, brain, and other peripheral tissues. Phosphatidylinositol 4,5-bisphosphate (PIP2) is a key direct activator of ion channels, including Kir channels. The gasotransmitter carbon monoxide has been shown to regulate Kir channel activity by altering channel-PIP2 interactions. Here, we tested in two cellular models the effects and mechanism of action of another gasotransmitter, hydrogen sulfide (H2S), thought to play a key role in cellular responses under ischemic conditions. Direct administration of sodium hydrogen sulfide as an exogenous H2S source and expression of cystathionine γ-lyase, a key enzyme that produces endogenous H2S in specific brain tissues, resulted in comparable current inhibition of several Kir2 and Kir3 channels. This effect resulted from changes in channel-gating kinetics rather than in conductance or cell-surface localization. The extent of H2S regulation depended on the strength of the channel-PIP2 interactions. H2S regulation was attenuated when channel-PIP2 interactions were strengthened and was increased when channel-PIP2 interactions were weakened by depleting PIP2 levels. These H2S effects required specific cytoplasmic cysteine residues in Kir3.2 channels. Mutation of these residues abolished H2S inhibition, and reintroduction of specific cysteine residues back into the background of the cytoplasmic cysteine-lacking mutant rescued H2S inhibition. Molecular dynamics simulation experiments provided mechanistic insights into how potential sulfhydration of specific cysteine residues could lead to changes in channel-PIP2 interactions and channel gating.
Adney,
A Critical Gating Switch at a Modulatory Site in Neuronal Kir3 Channels.
2015, Pubmed,
Xenbase
Adney,
A Critical Gating Switch at a Modulatory Site in Neuronal Kir3 Channels.
2015,
Pubmed
,
Xenbase Austgen,
Hydrogen sulfide augments synaptic neurotransmission in the nucleus of the solitary tract.
2011,
Pubmed Bian,
Role of hydrogen sulfide in the cardioprotection caused by ischemic preconditioning in the rat heart and cardiac myocytes.
2006,
Pubmed Bodhinathan,
Molecular mechanism underlying ethanol activation of G-protein-gated inwardly rectifying potassium channels.
2013,
Pubmed Chen,
A glutamate residue at the C terminus regulates activity of inward rectifier K+ channels: implication for Andersen's syndrome.
2002,
Pubmed Das,
Hydrogen sulfide mediates the cardioprotective effects of gene therapy with PKG-Iα.
2015,
Pubmed Du,
Characteristic interactions with phosphatidylinositol 4,5-bisphosphate determine regulation of kir channels by diverse modulators.
2004,
Pubmed
,
Xenbase Elrod,
Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function.
2007,
Pubmed Feng,
Hydrogen sulfide increases excitability through suppression of sustained potassium channel currents of rat trigeminal ganglion neurons.
2013,
Pubmed Gade,
Hydrogen sulfide as an allosteric modulator of ATP-sensitive potassium channels in colonic inflammation.
2013,
Pubmed Hibino,
Inwardly rectifying potassium channels: their structure, function, and physiological roles.
2010,
Pubmed Johansen,
Exogenous hydrogen sulfide (H2S) protects against regional myocardial ischemia-reperfusion injury--Evidence for a role of K ATP channels.
2006,
Pubmed Karschin,
IRK(1-3) and GIRK(1-4) inwardly rectifying K+ channel mRNAs are differentially expressed in the adult rat brain.
1996,
Pubmed Khademullah,
Depolarizing actions of hydrogen sulfide on hypothalamic paraventricular nucleus neurons.
2013,
Pubmed Krishnan,
H2S-Induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response.
2011,
Pubmed Kuksis,
Actions of a hydrogen sulfide donor (NaHS) on transient sodium, persistent sodium, and voltage-gated calcium currents in neurons of the subfornical organ.
2015,
Pubmed Logothetis,
Unifying Mechanism of Controlling Kir3 Channel Activity by G Proteins and Phosphoinositides.
2015,
Pubmed Luo,
Aggravation of seizure-like events by hydrogen sulfide: involvement of multiple targets that control neuronal excitability.
2014,
Pubmed McCune,
"Zipped Synthesis" by Cross-Metathesis Provides a Cystathionine β-Synthase Inhibitor that Attenuates Cellular H2S Levels and Reduces Neuronal Infarction in a Rat Ischemic Stroke Model.
2016,
Pubmed Mustafa,
H2S signals through protein S-sulfhydration.
2009,
Pubmed Mustafa,
Hydrogen sulfide as endothelium-derived hyperpolarizing factor sulfhydrates potassium channels.
2011,
Pubmed Paul,
H₂S signalling through protein sulfhydration and beyond.
2012,
Pubmed Paul,
H2S: A Novel Gasotransmitter that Signals by Sulfhydration.
2015,
Pubmed Pietri,
Hydrogen sulfide and hemeproteins: knowledge and mysteries.
2011,
Pubmed Plant,
SUMOylation of NaV1.2 channels mediates the early response to acute hypoxia in central neurons.
2016,
Pubmed Rohács,
Assaying phosphatidylinositol bisphosphate regulation of potassium channels.
2002,
Pubmed
,
Xenbase Rohács,
Distinct specificities of inwardly rectifying K(+) channels for phosphoinositides.
1999,
Pubmed
,
Xenbase Rohács,
Specificity of activation by phosphoinositides determines lipid regulation of Kir channels.
2003,
Pubmed
,
Xenbase Salloum,
Hydrogen sulfide and cardioprotection--Mechanistic insights and clinical translatability.
2015,
Pubmed Tucker,
Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor.
1997,
Pubmed
,
Xenbase Vivaudou,
Probing the G-protein regulation of GIRK1 and GIRK4, the two subunits of the KACh channel, using functional homomeric mutants.
1997,
Pubmed
,
Xenbase Wang,
Physiological implications of hydrogen sulfide: a whiff exploration that blossomed.
2012,
Pubmed Wei,
Hydrogen sulfide suppresses outward rectifier potassium currents in human pluripotent stem cell-derived cardiomyocytes.
2012,
Pubmed Whorton,
X-ray structure of the mammalian GIRK2-βγ G-protein complex.
2013,
Pubmed Whorton,
Crystal structure of the mammalian GIRK2 K+ channel and gating regulation by G proteins, PIP2, and sodium.
2011,
Pubmed
,
Xenbase Yi,
Yeast screen for constitutively active mutant G protein-activated potassium channels.
2001,
Pubmed
,
Xenbase Zerangue,
A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels.
1999,
Pubmed
,
Xenbase Zhang,
Selective phosphorylation modulates the PIP2 sensitivity of the CaM-SK channel complex.
2014,
Pubmed Zhang,
Detection of protein S-sulfhydration by a tag-switch technique.
2014,
Pubmed Zhang,
Hydrogen sulfide contributes to cardioprotection during ischemia-reperfusion injury by opening K ATP channels.
2007,
Pubmed
