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
2013 Nov 29;28848:34375-83. doi: 10.1074/jbc.M113.504324.
Show Gene links
Show Anatomy links
Independent contribution of extracellular proton binding sites to ASIC1a activation.
Krauson AJ
,
Rued AC
,
Carattino MD
.
???displayArticle.abstract???
Acid-sensing ion channels (ASICs) are a group of trimeric cation permeable channels gated by extracellular protons that are mainly expressed in the nervous system. Despite the structural information available for ASIC1, there is limited understanding of the molecular mechanism that allows these channels to sense and respond to drops in extracellular pH. In this report, we employed the substituted cysteine accessibility method and site-directed mutagenesis to examine the mechanism of activation of ASIC1a by extracellular protons. We found that the modification of E238C and D345C channels by MTSET reduced proton apparent affinity for activation. Furthermore, the introduction of positively charged residues at position 345 rendered shifted biphasic proton activation curves. Likewise, channels bearing mutations at positions 79 and 416 in the palm domain of the channel showed reduced proton apparent affinity and biphasic proton activation curves. Of significance, the effect of the mutations at positions 79 and 345 on channel activation was additive. E79K-D345K required a change to a pH lower than 2 for maximal activation. In summary, this study provides direct evidence for the presence of two distinct proton coordination sites in the extracellular region of ASIC1a, which jointly facilitate pore opening in response to extracellular acidification.
Baconguis,
Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes.
2012, Pubmed
Baconguis,
Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes.
2012,
Pubmed
Benson,
Heteromultimers of DEG/ENaC subunits form H+-gated channels in mouse sensory neurons.
2002,
Pubmed
Benson,
Acid-evoked currents in cardiac sensory neurons: A possible mediator of myocardial ischemic sensation.
1999,
Pubmed
Carattino,
Contribution of residues in second transmembrane domain of ASIC1a protein to ion selectivity.
2012,
Pubmed
,
Xenbase
Dawson,
Structure of the acid-sensing ion channel 1 in complex with the gating modifier Psalmotoxin 1.
2012,
Pubmed
Della Vecchia,
Gating transitions in the palm domain of ASIC1a.
2013,
Pubmed
,
Xenbase
Deval,
ASIC3, a sensor of acidic and primary inflammatory pain.
2008,
Pubmed
Duan,
Extracellular spermine exacerbates ischemic neuronal injury through sensitization of ASIC1a channels to extracellular acidosis.
2011,
Pubmed
Friese,
Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system.
2007,
Pubmed
Gautam,
Acid-sensing ion channels (ASICs) in mouse skeletal muscle afferents are heteromers composed of ASIC1a, ASIC2, and ASIC3 subunits.
2013,
Pubmed
Jasti,
Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH.
2007,
Pubmed
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
Liechti,
A combined computational and functional approach identifies new residues involved in pH-dependent gating of ASIC1a.
2010,
Pubmed
Lingueglia,
FMRFamide-gated sodium channel and ASIC channels: a new class of ionotropic receptors for FMRFamide and related peptides.
2006,
Pubmed
Mazzuca,
A tarantula peptide against pain via ASIC1a channels and opioid mechanisms.
2007,
Pubmed
Passero,
Conformational changes associated with proton-dependent gating of ASIC1a.
2009,
Pubmed
,
Xenbase
Paukert,
Candidate amino acids involved in H+ gating of acid-sensing ion channel 1a.
2008,
Pubmed
,
Xenbase
Price,
The mammalian sodium channel BNC1 is required for normal touch sensation.
2000,
Pubmed
Sutherland,
Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons.
2001,
Pubmed
Tolino,
Insights into the mechanism of pore opening of acid-sensing ion channel 1a.
2011,
Pubmed
,
Xenbase
Waldmann,
A proton-gated cation channel involved in acid-sensing.
1997,
Pubmed
,
Xenbase
Wemmie,
The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory.
2002,
Pubmed
Wemmie,
Acid-sensing ion channels: advances, questions and therapeutic opportunities.
2006,
Pubmed
Wemmie,
Overexpression of acid-sensing ion channel 1a in transgenic mice increases acquired fear-related behavior.
2004,
Pubmed
Weng,
Cell type-specific expression of acid-sensing ion channels in hippocampal interneurons.
2010,
Pubmed
Xiong,
Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels.
2004,
Pubmed
