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
2009 Dec 25;28452:36473-36481. doi: 10.1074/jbc.M109.055418.
Show Gene links
Show Anatomy links
Conformational changes associated with proton-dependent gating of ASIC1a.
Passero CJ
,
Okumura S
,
Carattino MD
.
???displayArticle.abstract???
Acid-sensing ion channels are proton-gated Na(+) channels expressed predominantly in neurons. How channel structure translates an environmental stimulus into changes in pore permeability remains largely undefined. The pore of ASIC1 is defined by residues in the second transmembrane domain (TM2), although a segment of the outer vestibule is formed by residues of TM1. We used the voltage clamp fluorometry technique to define the role of the region preceding TM2 (pre-TM2) in activation and desensitization of mouse ASIC1a. Oocytes expressing E425C channels labeled with Alexa Fluor 488 C5-maleimide showed a change in the emission of the fluorescent probe in response to extracellular acidification. The time course of the change in fluorescence correlated with activation but not desensitization of E425C channels. The fluorescence emission did not change following extracellular acidification in oocytes carrying an inactivating mutation (W287G/E425C), although these channels were labeled and expressed at the plasma membrane. Our data indicate that pore opening occurs in conjunction with a conformational rearrangement of the pre-TM2. We observed a change in the emission of the fluorescent probe when labeled E425C channels transition from the desensitized to the resting state. The substituted-cysteine-accessibility method was used to determine whether the pre-TM2 has different conformations in the resting and desensitized states. State-dependent changes in accessibility to 2-[(trimethylammonium)ethyl]methanethiosulfonate bromide modification were observed in oocytes expressing K421C, K422C, Y424C, and E425C channels. Our results suggest that the pre-TM2 of ASIC1a undergoes dynamic conformational rearrangements during proton-dependent gating.
Akopian,
A new member of the acid-sensing ion channel family.
2000, Pubmed
Akopian,
A new member of the acid-sensing ion channel family.
2000,
Pubmed
Babinski,
Molecular cloning and regional distribution of a human proton receptor subunit with biphasic functional properties.
1999,
Pubmed
,
Xenbase
Bannister,
Optical detection of rate-determining ion-modulated conformational changes of the ether-à-go-go K+ channel voltage sensor.
2005,
Pubmed
,
Xenbase
Benson,
Toward an understanding of the molecules that sense myocardial ischemia.
2001,
Pubmed
Bouzat,
Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel.
2004,
Pubmed
Bruns,
Epithelial Na+ channels are fully activated by furin- and prostasin-dependent release of an inhibitory peptide from the gamma-subunit.
2007,
Pubmed
,
Xenbase
Bubien,
Cation selectivity and inhibition of malignant glioma Na+ channels by Psalmotoxin 1.
2004,
Pubmed
Bässler,
Molecular and functional characterization of acid-sensing ion channel (ASIC) 1b.
2001,
Pubmed
,
Xenbase
Carattino,
Arachidonic acid regulates surface expression of epithelial sodium channels.
2003,
Pubmed
,
Xenbase
Cha,
Structural implications of fluorescence quenching in the Shaker K+ channel.
1998,
Pubmed
Cha,
Fluorescence techniques for studying cloned channels and transporters expressed in Xenopus oocytes.
1998,
Pubmed
,
Xenbase
Chen,
A sensory neuron-specific, proton-gated ion channel.
1998,
Pubmed
Coric,
The extracellular domain determines the kinetics of desensitization in acid-sensitive ion channel 1.
2003,
Pubmed
,
Xenbase
Coric,
Proton sensitivity of ASIC1 appeared with the rise of fishes by changes of residues in the region that follows TM1 in the ectodomain of the channel.
2005,
Pubmed
Cushman,
A conformation change in the extracellular domain that accompanies desensitization of acid-sensing ion channel (ASIC) 3.
2007,
Pubmed
García-Añoveros,
BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels.
1997,
Pubmed
Gründer,
A new member of acid-sensing ion channels from pituitary gland.
2000,
Pubmed
,
Xenbase
Immke,
Lactate enhances the acid-sensing Na+ channel on ischemia-sensing neurons.
2001,
Pubmed
Immke,
Protons open acid-sensing ion channels by catalyzing relief of Ca2+ blockade.
2003,
Pubmed
Immke,
ASIC3: a lactic acid sensor for cardiac pain.
2001,
Pubmed
Ishibashi,
Molecular cloning of a DEG/ENaC sodium channel cDNA from human testis.
1998,
Pubmed
Jasti,
Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH.
2007,
Pubmed
Javitch,
Mapping the binding-site crevice of the dopamine D2 receptor by the substituted-cysteine accessibility method.
1995,
Pubmed
Kapoor,
Knockdown of ASIC1 and epithelial sodium channel subunits inhibits glioblastoma whole cell current and cell migration.
2009,
Pubmed
Larsson,
Fluorometric measurements of conformational changes in glutamate transporters.
2004,
Pubmed
,
Xenbase
Li,
An intermediate state of the gamma-aminobutyric acid transporter GAT1 revealed by simultaneous voltage clamp and fluorescence.
2000,
Pubmed
,
Xenbase
Li,
Interaction of the aromatics Tyr-72/Trp-288 in the interface of the extracellular and transmembrane domains is essential for proton gating of acid-sensing ion channels.
2009,
Pubmed
,
Xenbase
Lingueglia,
A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells.
1997,
Pubmed
Liu,
Dynamic rearrangement of the outer mouth of a K+ channel during gating.
1996,
Pubmed
Mamet,
Proinflammatory mediators, stimulators of sensory neuron excitability via the expression of acid-sensing ion channels.
2002,
Pubmed
Mannuzzu,
Direct physical measure of conformational rearrangement underlying potassium channel gating.
1996,
Pubmed
,
Xenbase
Meinild,
Fluorescence studies of ligand-induced conformational changes of the Na(+)/glucose cotransporter.
2002,
Pubmed
,
Xenbase
Passero,
Plasmin activates epithelial Na+ channels by cleaving the gamma subunit.
2008,
Pubmed
,
Xenbase
Pathak,
Closing in on the resting state of the Shaker K(+) channel.
2007,
Pubmed
Paukert,
Candidate amino acids involved in H+ gating of acid-sensing ion channel 1a.
2008,
Pubmed
,
Xenbase
Paukert,
Identification of the Ca2+ blocking site of acid-sensing ion channel (ASIC) 1: implications for channel gating.
2004,
Pubmed
,
Xenbase
Price,
The DRASIC cation channel contributes to the detection of cutaneous touch and acid stimuli in mice.
2001,
Pubmed
Price,
Cloning and expression of a novel human brain Na+ channel.
1996,
Pubmed
,
Xenbase
Sluka,
Chronic hyperalgesia induced by repeated acid injections in muscle is abolished by the loss of ASIC3, but not ASIC1.
2003,
Pubmed
Sutherland,
Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons.
2001,
Pubmed
Ugawa,
Cloning and functional expression of ASIC-beta2, a splice variant of ASIC-beta.
2001,
Pubmed
,
Xenbase
Vila-Carriles,
Surface expression of ASIC2 inhibits the amiloride-sensitive current and migration of glioma cells.
2006,
Pubmed
Virkki,
Mapping conformational changes of a type IIb Na+/Pi cotransporter by voltage clamp fluorometry.
2006,
Pubmed
,
Xenbase
Voilley,
Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors.
2001,
Pubmed
Voilley,
Acid-sensing ion channels (ASICs): new targets for the analgesic effects of non-steroid anti-inflammatory drugs (NSAIDs).
2004,
Pubmed
Waldmann,
The mammalian degenerin MDEG, an amiloride-sensitive cation channel activated by mutations causing neurodegeneration in Caenorhabditis elegans.
1996,
Pubmed
Waldmann,
A proton-gated cation channel involved in acid-sensing.
1997,
Pubmed
,
Xenbase
Waldmann,
Molecular cloning of a non-inactivating proton-gated Na+ channel specific for sensory neurons.
1997,
Pubmed
Wemmie,
The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory.
2002,
Pubmed
Wemmie,
Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning.
2003,
Pubmed
Wemmie,
Overexpression of acid-sensing ion channel 1a in transgenic mice increases acquired fear-related behavior.
2004,
Pubmed
Yiangou,
Increased acid-sensing ion channel ASIC-3 in inflamed human intestine.
2001,
Pubmed
Zhang,
Gating of acid-sensitive ion channel-1: release of Ca2+ block vs. allosteric mechanism.
2006,
Pubmed
,
Xenbase
Zheng,
Patch-clamp fluorometry recording of conformational rearrangements of ion channels.
2003,
Pubmed
,
Xenbase
de Weille,
Identification, functional expression and chromosomal localisation of a sustained human proton-gated cation channel.
1998,
Pubmed
