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Nonclassical Ion Channels in Learning and Memory
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
Ze-Jie Lin, Xue Gu, Tian-Le Xu, Wei-Guang Li
ASICs are members of the sodium-selective cation channels belonging to the degenerin/epithelial sodium channel (DEG/ENaC) family, which can be activated by extracellular acidosis and are widely expressed in the mammalian nervous system (Waldmann et al. 1997). To date, at least six ASIC subunits (ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, and ASIC4; where a and b refer to splice variants) have been identified to be encoded by four genes (Asic1, Asic2, Asic3, and Asic4) (Kellenberger and Schild 2002, 2015; Wemmie, Price, and Welsh 2006; Wemmie, Taugher, and Kreple 2013). In mammals, there is a relative specificity of the distribution of various ASIC subtypes between the central and peripheral nervous systems (Krishtal 2003). While ASIC1a, ASIC2a, and ASIC2b are expressed in both peripheral and central nervous systems, ASIC1b and ASIC3 are primarily expressed in sensory neurons and non-neuronal tissues. As the most sensitive ion channel subtypes to extracellular acidosis, ASIC1a and ASIC3 have been proposed as ideal acid sensors in the central and peripheral nervous systems (Wemmie, Price, and Welsh 2006). ASIC3 is well positioned to be involved in multimodal sensory perception (Li and Xu 2011), especially in the acidosis-related chemosensation (Yagi et al. 2006; Birdsong et al. 2010; Yu et al. 2010; Peng et al. 2015; Marra et al. 2016; Stephan et al. 2018) and nociception (Chen et al. 2002; Sluka et al. 2003, 2007; Ikeuchi et al. 2008; Deval et al. 2008, 2011; Wang, Li, et al. 2013; Sluka and Gregory 2015) as well as mechanosensation (Price et al. 2001; Fromy et al. 2012; Jalalvand et al. 2016; Lin et al. 2016). By contrast, ASIC1a has been pathophysiologically implicated in ischemic neuronal death (Xiong et al. 2004; Gao et al. 2005; Pignataro, Simon, and Xiong 2007; Duan et al. 2011; Zeng et al. 2013; Wang, Zeng, et al. 2013; Wang et al. 2015, 2020) and chronic pain (Wu et al. 2004; Mazzuca et al. 2007; Duan et al. 2007, 2012; Bohlen et al. 2011; Diochot et al. 2012; Li et al. 2019). Of note, ASIC1a is also proposed as a novel synaptic receptor to cleft acidification and actively engaged in synaptic transmission and diverse types of synaptic plasticity (Kreple et al., 2014; Gonzalez-Inchauspe et al. 2017; Hill and Ben-Shahar 2018; Uchitel, Gonzalez Inchauspe, and Weissmann 2019; Mango and Nistico 2020). Due to the behavioral outputs associated with its synaptic action, ASIC1a has been shown to be of great importance for multiple forms of learning and memory. Here, we summarize these typical examples of ASIC1a involvement in learning and memory, which may advance our understanding of the physiological roles of this type of nonclassical ion channels.
An overview of carbonic anhydrases and membrane channels of synoviocytes in inflamed joints
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Acid-sensing ion channels (ASICs) mediate tissue acidosis by pH changes are known as voltage-insensitive, ligand-gated cation channels with protons53,54. The ASICs are associated with inflammatory pain, and especially ASIC1 and ASIC3 contribute to the musculoskeletal pain55. The ASIC3 is expressed in the sensory neurons that innervate the synovial joints by increasing the intracellular Ca2+ levels upon sensing a decrease of pH in the inflamed joint56,57. Synovial inflammation and inflammatory cytokine levels were increased that led to joint destruction in ASIC3–/– mice55. FLS were activated with the decrease in pH; the acidic environment increased the intracellular Ca2+ levels by ASIC357. Activation of FLS in acidic pH mediates the accumulation of inflammatory cytokines. In addition, activation of ASIC3 by acidic pH evokes Ca2+ signalling, which lead to the apoptosis of FLS by phosphorylation of the MAP kinase ERK in synovial inflammation; thus, it could be a blockade of synovial proliferation58. Activation of ASIC3 can be a therapeutic strategy for reducing inflammatory FLS level and subsequent disease progression in an inflamed joint.
Dual role of acid-sensing ion channels 3 in rheumatoid arthritis: destruction or protection?
Published in Immunopharmacology and Immunotoxicology, 2018
Gui-Mei Yu, Di Liu, Na Yuan, Bao-Hua Liu
Due to acid sensing property of these channels, their role in inflammatory joint disease viz., rheumatoid arthritis has been documented [15,16]. These channels are expressed in the cells of joints including chondrocytes, osteoblasts, osteoclasts, chondrocytes, synoviocytes, and epiphyseal plate [17–19]. Amongst different members of ASIC, ASIC3 has received significant attention due to its very high sensitivity to drop in extracellular pH [20]. A number of studies have shown that activation of ASIC3 increases joint inflammation [21–23]. On the other hand, some studies also suggest that ASIC3 functions decrease joint inflammation [15,16], suggesting the dual role of these channels. The present review discusses the dual role of these ASIC3 channels in joint inflammation with possible mechanisms.
Characteristics and the role of purinergic receptors in pathophysiology with focus on immune response
Published in International Reviews of Immunology, 2020
Marharyta Zyma, Rafał Pawliczak
One of the protective systems in organisms is nociceptive pain as a response for harmful stimuli, such as heat or chemical stimulus. However, this system works improperly in case of nervous system damage that can be result of diseases, for example diabetes, cancer, autoimmune diseases, and infections, which can effect in neuropathic pain. The symptoms of neuropathic pain are hyperalgesia, spontaneous pain, and allodynia. This pain has long term character and not only neuronal cells are involved in this condition, but also T cells, macrophages, monocytes and glial cells [151]. P2X3 receptors are expressed in the brainstem, in the primary nociceptive neurons and play a significant role in neuropathic pain. The study of the expression of P2X3 receptors in the astrocytes was conducted on Sprague-Dawley rats. According to the results, P2X3 was observed in the trigeminal caudal nucleus of astrocytes. Also, mGluR5 (metabotropic glutamate receptor 5) may be involved in regulation of the craniofacial neuropathic pain mediated by P2X3 receptors in astrocytes [152]. Besides, P2X3 receptors can associate with acid-sensing ion channels receptors (ASIC3) and form multiprotein structure. Stephan et al. [153] proposed that P2X3 receptor and ASIC3 may form not a heterodimeric, but a “cognate” receptor. Measurement of reversal potential elucidated that P2X3 and ASIC3 are able to switch their ionic permeabilities. After treatment with protons and α,β-meATP, ASIC3 receptor presented reversal potential characteristic for P2X3 receptor and vice versa. Similar outcomes have been obtained when protons and α,β-meATP were introduced separately [153]. Neuropathic pain is also a common complication of diabetes. Some studies show that P2X receptor antagonists have the ability to reduce the pain in diabetic rats and mice. In the study of streptozocin-induced diabetic rats the expression of P2X3 receptors was increased as well as an active form of NF-kB transcriptional factor. Besides, the inhibition of NF-kB led to suppression the P2X3 activities and diabetic pain weakening. Moreover, insulin treatment had the similar effects, which caused inhibition of the p65 and P2X3 expression. These observations can initiate the development of new treatment of neuropathic pain in diabetes patients [154]. Another strategy in treatment of neuropathic pain is microencapsulated Schwann cell transplantation. These immortal glial cells can produce different neurotrophic factors. This method was tested on a rat CCI (chronic constriction injury) model. As a result, the expression of P2X3 receptors was significantly decreased [155].