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 acid-sensing ion channel-1a (ASIC1a) is composed of 3 subunits and is activated by a decrease in extracellular pH. It plays an important role in diseases associated with a reduced pH and production of oxidants. Previous work showed that oxidants reduce ASIC1a currents. However, the effects on channel structure and composition are unknown. We found that ASIC1a formed inter-subunit disulfide bonds and the oxidant H(2)O(2) increased this link between subunits. Cys-495 in the ASIC1a C terminus was particularly important for inter-subunit disulfide bond formation, although other C-terminal cysteines contributed. Inter-subunit disulfide bonds also produced some ASIC1a complexes larger than trimers. Inter-subunit disulfide bond formation reduced the proportion of ASIC1a located on the cell surface and contributed to the H(2)O(2)-induced decrease in H(+)-gated current. These results indicate that channel function is controlled by disulfide bond formation between intracellular residues on distinct ASIC1a subunits. They also suggest a mechanism by which the redox state can dynamically regulate membrane protein activity by forming intracellular bridges.
Alvarez de la Rosa,
Distribution, subcellular localization and ontogeny of ASIC1 in the mammalian central nervous system.
2003, Pubmed
Alvarez de la Rosa,
Distribution, subcellular localization and ontogeny of ASIC1 in the mammalian central nervous system.
2003,
Pubmed Andrey,
Acid sensing ionic channels: modulation by redox reagents.
2005,
Pubmed Aracena-Parks,
Identification of cysteines involved in S-nitrosylation, S-glutathionylation, and oxidation to disulfides in ryanodine receptor type 1.
2006,
Pubmed Arias,
Amiloride is neuroprotective in an MPTP model of Parkinson's disease.
2008,
Pubmed Avshalumov,
H2O2 signaling in the nigrostriatal dopamine pathway via ATP-sensitive potassium channels: issues and answers.
2007,
Pubmed Bolton,
Localization and stabilization of ionotropic glutamate receptors at synapses.
2000,
Pubmed Bowen,
Proton MR spectroscopy of the brain in 14 patients with Parkinson disease.
1995,
Pubmed Cadiou,
Modulation of acid-sensing ion channel activity by nitric oxide.
2007,
Pubmed Chai,
A kinase-anchoring protein 150 and calcineurin are involved in regulation of acid-sensing ion channels ASIC1a and ASIC2a.
2007,
Pubmed Cho,
Potentiation of acid-sensing ion channels by sulfhydryl compounds.
2007,
Pubmed Chu,
ASIC1a-specific modulation of acid-sensing ion channels in mouse cortical neurons by redox reagents.
2006,
Pubmed Coryell,
Targeting ASIC1a reduces innate fear and alters neuronal activity in the fear circuit.
2007,
Pubmed Cumming,
Protein disulfide bond formation in the cytoplasm during oxidative stress.
2004,
Pubmed Emerit,
Neurodegenerative diseases and oxidative stress.
2004,
Pubmed Friese,
Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system.
2007,
Pubmed Ghafourifar,
Mitochondria in multiple sclerosis.
2008,
Pubmed Halliwell,
Reactive oxygen species and the central nervous system.
1992,
Pubmed Jasti,
Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH.
2007,
Pubmed Kamboj,
Receptor clustering: activate to accumulate?
1998,
Pubmed Kamsler,
Hydrogen peroxide as a diffusible signal molecule in synaptic plasticity.
2004,
Pubmed Kellenberger,
Epithelial sodium channel/degenerin family of ion channels: a variety of functions for a shared structure.
2002,
Pubmed Patel,
Mitochondrial dysfunction and oxidative stress: cause and consequence of epileptic seizures.
2004,
Pubmed Rosenbaum,
Dissecting intersubunit contacts in cyclic nucleotide-gated ion channels.
2002,
Pubmed
,
Xenbase Schulteis,
Intersubunit interaction between amino- and carboxyl-terminal cysteine residues in tetrameric shaker K+ channels.
1996,
Pubmed
,
Xenbase Siesjö,
Acidosis-related damage.
1996,
Pubmed Takahashi,
Hydrogen peroxide increases GABAergic mIPSC through presynaptic release of calcium from IP3 receptor-sensitive stores in spinal cord substantia gelatinosa neurons.
2007,
Pubmed Waldmann,
A proton-gated cation channel involved in acid-sensing.
1997,
Pubmed
,
Xenbase Waldmann,
H(+)-gated cation channels.
1999,
Pubmed Warner,
Oxidants, antioxidants and the ischemic brain.
2004,
Pubmed Wemmie,
Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning.
2003,
Pubmed Wemmie,
Acid-sensing ion channels: advances, questions and therapeutic opportunities.
2006,
Pubmed Wemmie,
The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory.
2002,
Pubmed Wemmie,
Overexpression of acid-sensing ion channel 1a in transgenic mice increases acquired fear-related behavior.
2004,
Pubmed Xiong,
Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels.
2004,
Pubmed Yermolaieva,
Extracellular acidosis increases neuronal cell calcium by activating acid-sensing ion channel 1a.
2004,
Pubmed Zha,
Acid-sensing ion channel 1a is a postsynaptic proton receptor that affects the density of dendritic spines.
2006,
Pubmed Ziemann,
Seizure termination by acidosis depends on ASIC1a.
2008,
Pubmed
