ACCN3
- Known as:
- ACCN3
- Catalog number:
- 000996A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ACCN3
Related genes to: ACCN3
- Gene:
- ASIC3 NIH gene
- Name:
- acid sensing ion channel subunit 3
- Previous symbol:
- ACCN3
- Synonyms:
- TNaC1, DRASIC
- Chromosome:
- 7q36.1
- Locus Type:
- gene with protein product
- Date approved:
- 1999-05-04
- Date modifiied:
- 2016-10-05
Related products to: ACCN3
Related articles to: ACCN3
- Acid-sensing ion channel 3 (ASIC3), a proton-gated cation channel predominantly expressed in primary afferent nociceptors, is an acidosis-related pain generator. Previous experiments suggested that ASIC3 is also involved in the generation of itch. However, mechanistic links between ASIC3 and itch, including the expression of ASIC3 in itch-mediating primary sensory neurons, remain unclear. We examined ASIC3 expression in these sensory neurons and then investigated whether mild acid stimulation could induce ASIC3-dependent itch without overt pain in mice. - Source: PubMed
Publication date: 2026/07/31
Shibata YasuhiroChaya RyosukeYokoi YutoKumamoto NatsukoUeda TakashiYousif Elamin Yousif ZobidahFujihara YoshitakaIkawa MasahitoYasui TakahiroUgawa Shinya - Cytokine interleukin-33 (IL-33) signaling in primary sensory neurons plays a crucial role in pain. However, the underlying molecular mechanisms remain poorly understood. Therefore, we investigated whether IL-33 signaling affects ion channels in nociceptive dorsal root ganglion (DRG) neurons. Herein, we reported that the application of IL-33 enhanced the electrophysiological activity of acid-sensing ion channels (ASICs). IL-33 dose-dependently increased acid-evoked ASIC currents in mouse DRG neurons. IL-33 enhanced the maximum responses of ASICs, whereas the sensitivity to acidic stimuli remained unaffected. This IL-33-induced enhancement of ASIC currents was dependent on suppression of the tumorigenicity 2 (ST2) receptors. The enhancing effect of IL-33 on ASIC currents was prevented by the p38 mitogen-activated protein kinase inhibitor SB202190, but not by the ERK inhibitor U0126 or the JNK inhibitor SP600125, indicating the effect was p38-dependent. Moreover, IL-33 potentiated the action potentials triggered by acidic stimuli. Finally, ASIC3-deficient mice displayed attenuated mechanical hyperalgesia induced by intraplantar or intramuscular injection of IL-33. Our findings revealed that IL-33 enhanced ASIC function via ST2 and the intracellular p38 signaling pathway, which might provide a promising therapeutic approach for pain treatment by targeting IL-33/ST2 signaling. - Source: PubMed
Publication date: 2026/08/07
Liu Ting-TingLi Xue-MeiQiu Chun-YuHu Wang-Ping - Leukotriene B4 (LTB4) is a lipid mediator generated from arachidonic acid. Studies have shown that LTB4 plays a role in the pain process. However, little is known about the underlying molecular and cellular mechanisms. The present data demonstrated a functional link between LTB4 and acid-sensing ion channels (ASICs) in mouse dorsal root ganglion (DRG) neurons. LTB4 potentiated acid-activated ASIC currents in a concentration-dependent and pH-independent manner. The potentiating effect of LTB4 on ASIC currents was mediated by BLT1 receptors but not by BLT2 receptors. The LTB4-induced potentiation of ASIC currents was prevented by the ERK1/2 inhibitor U0126 and the JNK inhibitor SP600125, but not by the p38 inhibitor SB202190, indicating involvement of intracellular ERK1/2 and JNK signaling. Moreover, LTB4 potentiated the burst of action potentials evoked by acidic stimuli in mouse DRG neurons. Behaviorally, intraplantar injection of LTB4 exaggerated spontaneous nociceptive behaviours evoked by subsequent acid challenge in WT mice, and developed attenuated mechanical hyperalgesia in ASIC3 KO mice. Our results suggested that LTB4 potentiated the electrophysiological activity of ASICs via BLT1 receptors as well as the ERK1/2 and JNK signaling pathways, which might open promising new perspectives for pain treatment associated with tissue acidification. - Source: PubMed
Publication date: 2026/07/29
Sun FeiYuan HuanWang ChenDu BeibeiLi Xue-MeiLiu Ting-TingQiu Chun-YuHu Wang-Ping - Acid-sensing ion channels (ASICs) are proton-gated sodium channels encoded by four genes in mammals. The ASIC3 isoform is widely expressed and plays a critical role in pain signaling and inflammatory responses. Despite a high degree of sequence homology between rat and human ASIC3 orthologs, they exhibit pronounced functional differences. Notably, rat ASIC3 undergoes steady-state desensitization (SSD) at extracellular pH values of 7.1-7.0, whereas human ASIC3 is largely desensitized at physiological pH (7.4-7.3), underscoring substantial interspecies divergence with important translational implications. In this study, we systematically investigated the functional properties of rat and human ASIC3 channels using concatemeric constructs that enable precise control over subunit stoichiometry and gene order within engineered trimeric assemblies. Using whole-cell electrophysiology, we show that homomeric concatemeric channels (r-r-r and h-h-h) closely recapitulate the biophysical properties of their respective wild-type channels. Substitution of a single subunit at the N-terminal position of the concatemer with an ASIC3 ortholog produced minimal functional perturbations and yielded channel properties most similar to those of the corresponding homomeric channel. In contrast, replacement of the C-terminal subunit resulted in the most pronounced shifts in pHSSD values and significant alterations in activation kinetics and current characteristics, indicating that functional properties of ASIC3 concatemers are strongly influenced by subunit position within the construct. Together, these findings demonstrate that both subunit composition and positional arrangement contribute to the functional behavior of engineered ASIC3 concatemers and provide a useful experimental framework for analyzing interspecies differences between rat and human ASIC3 channels. The results also highlight important limitations of concatemeric approaches, including the potential emergence of non-native channel properties in certain construct configurations. - Source: PubMed
Publication date: 2026/06/30
Osmakov Dmitry IKorolkova Yuliya VMaleeva Ekaterina ELogashina Yulia ADubodel Elisaveta SLubova Kseniya IKoshelev Sergey GAndreev Yaroslav AKozlov Sergey A - To elucidate the mechanism by which Resveratrol (Res) ameliorates hypertrophic scar (HS) formation by targeting acid-sensing ion channel 3 (ASIC3) to modulate macrophage-fibroblast (FB) crosstalk. A rabbit-ear HS model was established in vivo. Hematoxylin-eosin (H&E) staining, Masson staining, immunofluorescence (IF), Western blot (WB), and quantitative real-time PCR (RT-qPCR) were used to assess the effects of Res on scar hyperplasia, collagen deposition, FB activation, and macrophage polarization. In vitro, FB activation was stimulated by combined treatment with TGF-β1 and lactic acid, and a Transwell co-culture system comprising FB and human monocyte-derived M0 macrophages was established. Scratch assay, FCM, IF, and WB were performed to assess the impacts of Res on FB activation, migration, and macrophage polarization. Additionally, ASIC3 gene knockout experiments were conducted both in vivo and in vitro to confirm the mechanism underlying Res-mediated HS improvement. In vitro, Res significantly inhibited FB migration in a dose-dependent manner and downregulated the protein expression of α-SMA, COL1A1, COL3A1, reduced M-CSF secretion, suppressed macrophage polarization toward the M2 phenotype, and decreased TGF-β1 mRNA expression. It also blocked activation of the PI3K/Akt signaling pathway downstream of ASIC3. These effects were completely abolished after ASIC3 gene knockdown. In vivo, Res significantly reduced the scar elevation index (SEI) in rabbit-ear HS. It improved collagen fiber arrangement and decreased collagen deposition. It markedly inhibited M2 macrophage polarization and TGF-β1 mRNA expression. After ASIC3 knockout, the anti-HS effects of Res, as well as its regulatory effects on macrophage polarization and fibrotic factors, were abrogated. Res ameliorates HS by inhibiting ASIC3 expression. This disrupts the ASIC3-M-CSF-TGF-β1 positive feedback loop. It restores the balance of macrophage polarization, inhibits FB activation, reduces abnormal collagen deposition, and ultimately attenuates HS formation. - Source: PubMed
Publication date: 2026/06/08
Sun ZiliHuang SuzhouLu XingxingZhang YihengDing XinMa TianleYuan BingfengYu ShanWu Li