ACCN2
- Known as:
- ACCN2
- Catalog number:
- 000995A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ACCN2
Related genes to: ACCN2
- Gene:
- ASIC1 NIH gene
- Name:
- acid sensing ion channel subunit 1
- Previous symbol:
- ACCN2
- Synonyms:
- BNaC2, hBNaC2
- Chromosome:
- 12q13.12
- Locus Type:
- gene with protein product
- Date approved:
- 1997-09-05
- Date modifiied:
- 2016-09-30
Related products to: ACCN2
Related articles to: ACCN2
- Animal models of inflammatory pain frequently rely on local administration of irritants that trigger acute inflammation and hypersensitivity. Lipopolysaccharide (LPS) is a well-established activator of innate immune pathways. Subcutaneous (intraplantar) injection of LPS into the hind paw produces a localized inflammatory reaction characterized by swelling, cellular infiltration, and increased mechanical and thermal sensitivity. Acid-sensing ion channels (ASICs) are key contributors to nociceptive signaling; however, their presence and regulation at the level of peripheral terminals, particularly in the skin, remain insufficiently characterized. We previously showed that formalin-induced acute pain increases ASIC1a expression in the central nervous system and peripheral dorsal root ganglia (DRGs). In this study, using the LPS paw model in both male and female mice, we demonstrate a robust upregulation of ASIC1a directly within inflamed paw tissue, together with changes in lumbar dorsal root ganglia (DRGs), which contain the somata of sensory neurons innervating the paw. We further show that ASIC1a upregulation is associated with paw edema, ERK activation, miRNA-dependent regulatory mechanisms, and the development of behavioral hypersensitivity induced by LPS. Importantly, local pharmacological blockade of ASIC1a with subcutaneous PcTx-1 attenuated both mechanical and thermal hypersensitivity. Together, our findings identify inflamed peripheral tissue as an important site of ASIC1a regulation during LPS-induced inflammation and provide new insight into the molecular mechanisms governing ASIC1a expression in inflammatory pain, supporting further exploration of ASIC1a-targeted therapeutic strategies. - Source: PubMed
Publication date: 2026/07/27
Montes Mayra MicaelaSalinas Castellanos Libia CatalinaGuidobono Juan SantiagoLacave MarielaDe Lucca RominaWeissmann Carina - Acid-sensing ion channels (ASICs) are typically activated by acidic environments and contribute to nociception and synaptic plasticity. ASIC1a is the most abundant subunit in the central nervous system and forms homomeric channels permeable to Na and Ca, making it a compelling therapeutic target for acidotic pathologies including stroke and traumatic brain injury. However, a complete conformational library of human ASIC1a has yet to be described. Here we show that human ASIC1a adopts six major conformations, resolved by cryo-electron microscopy across a pH range between 8.5 and 5.7 and in the presence of a toxin agonist and a gating-modifying amino acid substitution. These major conformations establish linear transmembrane helices to be associated with an open state, delineate mechanistic differences between proton and toxin activation and demonstrate that desensitization involves unexpected conformational diversity in the transmembrane domain. Together, they provide a three-dimensional framework to integrate previous structure-function studies on ASIC. - Source: PubMed
Publication date: 2026/07/16
Cahill JamesHartfield Kimberly AHeusser Stephanie AndreaRitter NadinePoulsen Mette HomannYoshioka CraigPless Stephan AlexanderBaconguis Isabelle - Traumatic brain injury (TBI) is a neurological disorder that severely affects health and function. Acid-sensing ion channels 1a (ASIC1a), a proton-gated cation channel permeable to Na and Ca, has been implicated in chronic neurodegeneration after TBI. However, its specific role in post-TBI neuroinflammation remains poorly defined. In this study, we investigated the mechanistic involvement of ASIC1a in neuronal pyroptosis following TBI. - Source: PubMed
Liang JiaweiChen PengZhao YangyangLei PanLi YulongZhang YichenCai Jia-HongJiang Yong-AnZhang YanCheng Shiqi - Acid-sensing ion channels (ASICs) are proton-gated ion channels involved in synaptic transmission, pain, and ischaemic injury. Nb.C1 is a nanobody which targets human ASIC1a and was first described as a silent binder, but its broader pharmacological profile has not been resolved. Here, we show that Nb.C1 potentiates acid-evoked peak currents of both hASIC1a and hASIC1b by increasing current amplitude relative to control, with EC values of ∼55 nM and ∼73 nM, respectively. This activity is consistent with sequence conservation of the thumb domain between these isoforms, which serves as the Nb.C1 binding site. Nb.C1 potentiates hASIC1a without altering the pH of activation, whereas at hASIC1b it shifts the pH-dependence of activation to more alkaline values by 0.38 pH units. Fusion of Nb.C1 to the ASIC1a-inhibiting peptide psalmotoxin 1 (PcTx1) generates a bivalent molecule, Nb.C1-PcTx1, which retains PcTx1's mechanism of inhibition at hASIC1a but exhibits markedly prolonged activity consistent with increased avidity. At hASIC1b, Nb.C1-PcTx1 produces a large 1.12 pH unit alkaline shift in the pH dependence of activation and sustained inward currents near physiological pH with slow washout. Together, these results demonstrate that Nb.C1 acts as a nanomolar potentiator of both human ASIC1a and ASIC1b and that fusion to PcTx1 markedly prolongs ligand activity through avidity, resulting in persistent off-target modulation at ASIC1b. - Source: PubMed
Publication date: 2026/04/07
Golder MimiButcher Neville JNaughton Jennifer DLiu JunyuCrawford TheoRash Lachlan DMobli MehdiCristofori-Armstrong Ben - Effective host defense against pathogens requires coordinated behavioral and immune responses, yet the mechanisms that couple epithelial sensing to these systemic defenses remain poorly understood. Here, we identify a proton-mediated gut-to-neuron signaling pathway that orchestrates host defense in C. elegans. Intestinal pathogens stimulate mechanosensitive Ca influx into intestinal epithelial cells (IECs) through the TRP channel GON-2, activating the Na/H exchanger NHX-6 via the calmodulin CMD-1 to drive basolateral proton release. These protons activate cholinergic motor neurons through the acid-sensing ion channel ASIC-1, enhancing cholinergic transmission to promote both pathogen avoidance and intestinal innate immunity. Notably, mouse NHE1 and ASIC1a can functionally substitute for their nematode counterparts. Together, these findings demonstrate a role for proton signaling in gut-to-neuron communication, revealing a potentially conserved mechanism that links epithelial sensing to neuroimmune defense. - Source: PubMed
Publication date: 2026/03/27
Lei YingZhan XuChen ChaoLiu YuxinWang YingLiu Ping