Ask about this productRelated genes to: ACCN2 antibody
- 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 antibody
Related articles to: ACCN2 antibody
- 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 - A variety of studies show the involvement of acid-sensing ion channel 1a (ASIC1a) in the modulation of stress, however, the precise underlying mechanisms remain unclear. In this study, we provided evidence that ASIC1a, the Ca-permeable cationic ion channel, was co-expressed with corticotropin-releasing hormone (CRH) in the hypothalamic paraventricular nucleus (PVN). Downregulation of ASIC1a in the PVN CRH neuron decreased the hypothalamic-pituitary-adrenal (HPA) axis activity, which further ameliorated anxiety- and depression-related behaviors by reducing CRH neuron activity. In vitro, activation of ASIC1a elevated the intracellular Ca concentration and promoted the expression of CRH by activating Ca/CaMKII/c-Fos signaling pathways. This study reveals a novel mechanism of the modulation of negative mood by ASIC1a and suggests a potential novel therapeutic target for stress-related diseases. - Source: PubMed
Publication date: 2026/03/19
Yue JiayinZhang QilunWang MengyuanYao XuelinWang MengtianLiu LingHuang ZhaohuanXing YanYan JinlingYan ZihuiSong Xing-LeiWang Wei - Our previous studies have shown that acid-sensitive ion channel 1a (ASIC1a) promotes lipopolysaccharide (LPS)-induced acute lung injury (ALI), but the exact mechanism is unclear. This study explores the potential mechanism by which ASIC1a promotes ALI and provides new ideas for the development of new drugs. - Source: PubMed
Publication date: 2026/03/13
Zhang AnqiZhu YueqinChen HaoyangLv XiaoyuZhang TingtingRen RuohanWang YuyanXu HuXu ZhouLi ZihaoQian ShishunZhang JingrongLi MengxueHu XiaojieCao ChunAbou-Elnour AmiraDing ZhenxingWang JiajiaHuang Yan - Pulmonary hypertension (PH) is a progressive vascular disease driven by pulmonary arterial remodeling, characterized by cellular hyperproliferation, resistance to apoptosis, and phenotypic plasticity. Our laboratory has shown that the proton-gated cation channel, acid-sensing ion channel 1a (ASIC1a), is essential for the development of chronic hypoxia (CH)-induced PH in rodents. Importantly, ASIC1a activation occurs without changes in total ASIC1a levels but reflects a hypoxia-dependent redistribution to the plasma membrane in pulmonary arterial smooth muscle cells (PASMCs). In neurons, mitochondrial-localized ASIC1a (mtASIC1a) contributes to oxidative stress-induced mitochondrial membrane potential (ΔΨm) depolarization and apoptosis. Although mtASIC1a has not been described in vascular cells, its role in PASMCs may be relevant to mitochondrial dysfunction and apoptosis resistance in PH. We hypothesize that mtASIC1a is a crucial regulator of PASMC mitochondrial homeostasis, and its loss following CH promotes mitochondrial dysfunction and apoptosis resistance. Consistent with this, mtASIC1a localization was decreased in PASMCs and intrapulmonary arteries from CH rats compared with controls. Functionally, PASMCs from CH rats or knockout mice exhibited ΔΨm hyperpolarization, elevated mitochondrial Ca and superoxide, impaired mitophagy, and reduced cleaved caspase-3. Transmission electron microscopy revealed mitochondrial morphological changes, including increased size and circularity, decreased aspect ratio, and reduced mitochondrial number per cell, whereas fusion/fission proteins remained largely unchanged. Lentiviral restoration of mtASIC1a prevented ΔΨm hyperpolarization and restored caspase-3 cleavage. These findings identify mtASIC1a as a novel regulator of mitochondrial function in PASMCs, where its loss following CH promotes ΔΨm hyperpolarization, impaired mitophagy, and resistance to apoptosis. This study identifies mitochondrial acid-sensing ion channel 1a (mtASIC1a) as a novel regulator of mitochondrial homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Critically, mtASIC1a deficiency in PASMCs following in vivo chronic hypoxia or genetic deletion promotes mitochondrial membrane potential (ΔΨm) hyperpolarization, Ca and superoxide (O) accumulation, impaired mitophagy, and caspase inhibition. Restoring mtASIC1a by lentiviral transduction prevents ΔΨm hyperpolarization and restores caspase cleavage, highlighting its importance in mitochondrial signaling and hypoxic pulmonary hypertension pathophysiology. - Source: PubMed
Publication date: 2026/02/25
Tuineau Megan NHerbert Lindsay MMedina Heaven ENaik Jay SResta Thomas CJernigan Nikki L