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Acid-sensing ion channels

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https://www.readbyqxmd.com/read/29209451/mir-149-reduces-while-let-7-elevates-asic1a-expression-in-vitro
#1
Yu-Qing Jiang, Xiang-Ming Zha
Acid-sensing ion channel 1a (ASIC1a) is the key subunit that determines acid-activated currents in neurons. ASIC1a is important for neural plasticity, learning, and for multiple neurological diseases, including stroke, multiple sclerosis, and traumatic injuries. These findings underline the importance for better defining mechanisms that regulate ASIC1a expression. During the past decade, microRNA has emerged as one important group of regulatory molecules in controlling protein expression. However, little is known about whether microRNA regulates ASIC1a...
2017: International Journal of Physiology, Pathophysiology and Pharmacology
https://www.readbyqxmd.com/read/29199826/luminescent-3d-lanthanide-cadmium-heterometal-organic-frameworks-with-chemical-stability-and-selective-luminescent-sensing
#2
Ling Ding, Le-Hui Liu, Qing Shi, Yan-Qiong Sun, Yong-Jiang Wang, Yi-Ping Chen
Four novel three-dimensional (3D) 4d-4f heterometal-organic compounds, [LnCd2(Pbc)4(Meimdc)(H2O)]·3H2O (Ln = Eu, 1a; Tb, 1b; Sm, 1c; Dy, 1d) (HPbc = 4-(4-pyridinyl)benzoic acid; H3Meimdc = 2-methyl-1H-4,5-imidazole-dicarboxylic acid), have been successfully prepared by a hydrothermal method. All the compounds are isostructural and show three-dimensional microporous pillar-layered structures with uncoordinated carboxylate sites hung in the channels. Compound 1a possesses excellent chemical stability. The luminescent investigations show that compounds 1a, 1b, 1c, and 1d display the characteristic emission bands of Ln3+ ions...
December 4, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/29197566/local-subcutaneous-injection-of-chlorogenic-acid-inhibits-the-nociceptive-trigeminal-spinal-nucleus-caudalis-neurons-in-rats
#3
Kaede Kakita, Hirona Tsubouchi, Mayu Adachi, Shiori Takehana, Yoshihito Shimazu, Mamoru Takeda
Acute administration of chlorogenic acid (CGA) in vitro was recently shown to modulate potassium channel conductance and acid-sensing ion channels (ASICs) in the primary sensory neurons; however, in vivo peripheral effects of CGA on the nociceptive mechanical stimulation of trigeminal neuronal activity remains to be determined. The present study investigated whether local administration of CGA in vivo attenuates mechanical stimulation-induced excitability of trigeminal spinal nucleus caudalis neuronal (SpVc) activity in rats...
November 29, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/29196182/peripheral-5-ht3-mediates-mirror-image-pain-by-a-cross-talk-with-acid-sensing-ion-channel-3
#4
Yeu-Shiuan Su, Hao-Ruei Mei, Chun-Hung Wang, Wei-Hsin Sun
Mirror-image pain (MIP), which occurs along with complex regional pain syndrome, rheumatoid arthritis and chronic migraine, is characterized by increased pain sensitivity of healthy body regions other than the actual injured or inflamed sites. A high level of peripheral inflammation may activate central or peripheral glia, triggering mirror-image pain. However, which receptors mediate inflammatory signals to contribute glial activation remains unclear. Intraplantarly injecting mice with 5-hydroxytryptamine (5-HT) or acidic buffer (proton) caused only unilateral hyperalgesia, but co-injection of 5-HT/acid induced bilateral hyperalgesia (MIP)...
November 28, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29190977/ppar-%C3%AE-acutely-inhibits-functional-activity-of-asics-in-rat-dorsal-root-ganglion-neurons
#5
Jing Wu, Jia-Jia Wang, Ting-Ting Liu, Yi-Mei Zhou, Chun-Yu Qiu, Ding-Wen Shen, Wang-Ping Hu
Peroxisome proliferator-activated receptor-α (PPAR-α), a lipid activated transcription factor of nuclear hormone receptor superfamily, can relieve pain through a rapid-response mechanism. However, little is known about the underlying mechanism. Herein, we report that PPAR-α activation acutely inhibits the functional activity of acid-sensing ion channels (ASICs), key sensors for extracellular protons, in rat dorsal root ganglion (DRG) neurons. Pre-application of PPAR-α agonist GW7647 for 2 min decreased the amplitude of proton-gated currents mediated by ASICs in a concentration-dependent manner...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29172994/amiloride-does-not-protect-retinal-nerve-fibre-layer-thickness-in-optic-neuritis-in-a-phase-2-randomised-controlled-trial
#6
Justin B McKee, Charles L Cottriall, John Elston, Simon Epps, Nikos Evangelou, Stephen Gerry, Christopher Kennard, Yazhuo Kong, Abigail Koelewyn, Wilhelm Kueker, Maria Isabel Leite, Jacqueline Palace, Matthew Craner
BACKGROUND: Recent basic and clinical evidence suggests amiloride may be neuroprotective in multiple sclerosis (MS) through the blockade of the acid sensing ion channel (ASIC). OBJECTIVE: To examine the neuroprotective efficacy of amiloride in acute optic neuritis (ON). METHODS: A total of 48 patients were recruited to a phase 2, double blind, single site, randomised controlled trial. Scanning laser polarimetry (GDx) at 6 months was the primary outcome measure and optical coherence tomography (OCT) and visual and electrophysiological measures were secondary outcome measures...
November 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29171028/the-mechanosensitive-piezo1-channel-structural-features-and-molecular-bases-underlying-its-ion-permeation-and-mechanotransduction
#7
Yubo Wang, Bailong Xiao
The evolutionarily conserved Piezo family of proteins, including Piezo1 and Piezo2, encodes the long-sought-after mammalian mechanosensitive cation channels that play critical roles in various mechanotransduction processes such as touch, pain, proprioception, vascular development and blood pressure regulation. Mammalian Piezo proteins contain over 2500 amino acids with numerous predicted transmembrane segments, and do not bear sequence homology with any known class of ion channels. Thus, it is imperative, but challenging, to understand how they serve as effective mechanotransducers for converting mechanical force into electrochemical signals...
November 24, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29141196/asic2a-overexpression-enhances-the-protective-effect-of-pctx1-and-apetx2-against-acidosis-induced-articular-chondrocyte-apoptosis-and-cytotoxicity
#8
Ren-Peng Zhou, Wen-Lin Ni, Bei-Bei Dai, Xiao-Shan Wu, Zhi-Sen Wang, Ya-Ya Xie, Zhi-Qiang Wang, Wei-Jie Yang, Jin-Fang Ge, Wei Hu, Fei-Hu Chen
Acid hydrarthrosis is another important pathological character in rheumatoid arthritis (RA), and acid-sensing ion channel 1a (ASIC1a) plays a destructive role in acidosis-induced articular chondrocyte cytotoxicity. Recently, ASIC2a has been reported to possess neuroprotective effect on acidosis-induced injury of neuronal cells. However, whether ASIC2a has an enhanced effect on the protective effect of blocking ASIC1a and ASIC3 against acid-induced chondrocyte apoptosis is still unclear. The aim of present study was to investigate the chondroprotective effect of ASIC2a with PcTx1 (ASIC1a specific blocker) and APETx2 (ASIC3 specific blocker) on acidosis-induced chondrocyte apoptosis...
November 13, 2017: Gene
https://www.readbyqxmd.com/read/29134638/inhibition-of-acid-sensing-ion-channels-by-diminazene-and-apetx2-evoke-partial-and-highly-variable-antihyperalgesia-in-a-rat-model-of-inflammatory-pain
#9
Jia Yu Peppermint Lee, Natalie J Saez, Ben Cristofori-Armstrong, Raveendra Anangi, Glenn F King, Maree T Smith, Lachlan D Rash
BACKGROUND AND PURPOSE: Acid-sensing ion channels (ASICs) are primary acid sensors in mammals, with the ASIC1b and ASIC3 subtypes being involved in peripheral nociception. The antiprotozoal drug diminazene is a moderately potent ASIC inhibitor but its analgesic activity has not been assessed. EXPERIMENTAL APPROACH: We determined the ASIC subtype selectivity of diminazene and the mechanism by which it inhibits ASICs using voltage-clamp electrophysiology of Xenopus oocytes expressing ASICs 1-3...
November 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29129203/naadp-evoked-ca-2-signals-through-two-pore-channel-1-require-arginine-residues-in-the-first-s4-s5-linker
#10
Sandip Patel, Dev Churamani, Eugen Brailoiu
Two-pore channels (TPCs) are two-domain members of the voltage-gated ion channel superfamily that localize to acidic organelles. Their mechanism of activation (ligands such as NAADP/PI(3,5)P2 versus voltage) and ion selectivity (Ca(2+) versus Na(+)) is debated. Here we report that a cluster of arginine residues in the first domain required for selective voltage-gating of TPC1 map not to the voltage-sensing fourth transmembrane region (S4) but to a cytosolic downstream region (S4-S5 linker). These residues are conserved between TPC isoforms suggesting a generic role in TPC activation...
December 2017: Cell Calcium
https://www.readbyqxmd.com/read/29123030/the-nonproton-ligand-of-acid-sensing-ion-channel-3-activates-mollusk-specific-fanac-channels-via-a-mechanism-independent-of-native-fmrfamide-peptide
#11
Xiao-Na Yang, You-Ya Niu, Yan Liu, Yang Yang, Wang Jin, Xiao-Yang Cheng, Hong Liang, Heng-Shan Wang, You-Min Hu, Xiang-Yang Lu, Michael X Zhu, Tian-Le Xu, Yun Tian, Ye Yu
The degenerin/epithelial sodium channel (DEG/ENaC) superfamily of ion channels contains subfamilies with diverse functions that are fundamental to many physiological and pathological processes, ranging from synaptic transmission to epileptogenesis. The absence in mammals of some DEG/ENaCs subfamily orthologs such as FMRFamide peptide-activated sodium channels (FaNaCs), which have been identified only in mollusks, indicates that the various subfamilies diverged early in evolution. We recently reported that the nonproton agonist 2-guanidine-4-methylquinazoline (GMQ) activates acid-sensing ion channels (ASICs), a DEG/ENaC subfamily mainly in mammals, in the absence of acidosis...
November 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29111855/neuroprotective-effects-of-inhibitors-of-acid-sensing-ion-channels-asics-in-optic-nerve-crush-model-in-rodents
#12
Dorota L Stankowska, Brett H Mueller, Hidehiro Oku, Tsunehiko Ikeda, Adnan Dibas
PURPOSE: The purpose of the current study was to assess the potential involvement of acid-sensing ion channel 1 (ASIC1) in retinal ganglion cell (RGC) death and investigate the neuroprotective effects of inhibitors of ASICs in promoting RGC survival following optic nerve crush (ONC). RESULTS: ASIC1 protein was significantly increased in optic nerve extracts at day 7 following ONC in rats. Activated calpain-1 increased at 2 and 7 days following ONC as evidenced by increased degradation of α-fodrin, known substrate of calpain...
November 7, 2017: Current Eye Research
https://www.readbyqxmd.com/read/29099043/involvement-of-opioid-system-trpm8-and-asic-receptors-in-antinociceptive-effect-of-arrabidaea-brachypoda-dc-bureau
#13
Vinícius Peixoto Rodrigues, Cláudia Quintino da Rocha, Larissa Lucena Périco, Raquel de Cássia Dos Santos, Rie Ohara, Catarine Massucato Nishijima, Emerson Ferreira Queiroz, Jean-Luc Wolfender, Lúcia Regina Machado da Rocha, Adair Roberto Soares Santos, Wagner Vilegas, Clélia Akiko Hiruma-Lima
Arrabidaea brachypoda (DC) Bureau is a medicinal plant found in Brazil. Known as "cipó-una", it is popularly used as a natural therapeutic agent against pain and inflammation. This study evaluated the chemical composition and antinociceptive activity of the dichloromethane fraction from the roots of A. brachypoda (DEAB) and its mechanism of action. The chemical composition was characterized by high-performance liquid chromatography, and this fraction is composed only of dimeric flavonoids. The antinociceptive effect was evaluated in formalin and hot plate tests after oral administration (10-100 mg/kg) in male Swiss mice...
November 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29070491/rhoa-increases-asic1a-plasma-membrane-localization-and-calcium-influx-in-pulmonary-arterial-smooth-muscle-cells-following-chronic-hypoxia
#14
Lindsay M Herbert, Thomas C Resta, Nikki L Jernigan
Increases in pulmonary arterial smooth muscle cell (PASMC) intracellular Ca(2+) levels and enhanced RhoA/Rho kinase-dependent Ca(2+) sensitization are key determinants of PASMC contraction, migration, and proliferation accompanying the development of hypoxic pulmonary hypertension. We have previously shown acid sensing ion channel 1a (ASIC1a)-mediated Ca(2+) entry in PASMC is an important constituent of the active vasoconstriction, vascular remodeling, and right ventricular hypertrophy associated with hypoxic pulmonary hypertension...
October 25, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29058095/potentiation-and-block-of-asic1a-by-memantine
#15
Vasiliy Y Shteinikov, Tatiana B Tikhonova, Vyacheslav S Korkosh, Denis B Tikhonov
Acid-sensing ion channels (ASICs) are modulated by various classes of ligands, including the recently described hydrophobic monoamines, which inhibit and potentiate ASICs in a subunit-specific manner. In particular, memantine inhibits ASIC1a and potentiates ASIC2a homomers. The aim of the present work was to characterize action mechanism of memantine on recombinant ASIC1a expressed in CHO (Chinese hamster ovary) cells. We have demonstrated that effect of memantine on ASIC1a strongly depends on membrane voltage, conditioning pH value and application protocol...
October 20, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/29057936/glioblastoma-cancer-stem-cell-lines-express-functional-acid-sensing-ion-channels-asic1a-and-asic3
#16
Yuemin Tian, Pia Bresenitz, Anna Reska, Laila El Moussaoui, Christoph Patrick Beier, Stefan Gründer
Acidic microenvironment is commonly observed in tumour tissues, including glioblastoma (GBM), the most aggressive and lethal brain tumour in adults. Acid sensing ion channels (ASICs) are neuronal voltage-insensitive sodium channels, which are sensors of extracellular protons. Here we studied and functionally characterized ASICs in two primary glioblastoma stem cell lines as cell culture models. We detected transcripts of the ACCN2 and ACCN3 genes, coding for ASIC1 and ASIC3, respectively, but not transcripts of ACCN1 (coding for ASIC2)...
October 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29056828/acid-sensing-ion-channels-as-potential-therapeutic-targets-in-neurodegeneration-and-neuroinflammation
#17
REVIEW
Audrey Ortega-Ramírez, Rosario Vega, Enrique Soto
Acid-sensing ion channels (ASICs) are a family of proton-sensing channels that are voltage insensitive, cation selective (mostly permeable to Na(+)), and nonspecifically blocked by amiloride. Derived from 5 genes (ACCN1-5), 7 subunits have been identified, 1a, 1b, 2a, 2b, 3, 4, and 5, that are widely expressed in the peripheral and central nervous system as well as other tissues. Over the years, different studies have shown that activation of these channels is linked to various physiological and pathological processes, such as memory, learning, fear, anxiety, ischemia, and multiple sclerosis to name a few, so their potential as therapeutic targets is increasing...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/29054733/disrupted-ionic-homeostasis-in-ischemic-stroke-and-new-therapeutic-targets
#18
REVIEW
Hui-Jie Hu, Mingke Song
BACKGROUND: Stroke is a leading cause of long-term disability. All neuroprotectants targeting excitotoxicity have failed to become stroke medications. In order to explore and identify new therapeutic targets for stroke, we here reviewed present studies of ionic transporters and channels that are involved in ischemic brain damage. METHOD: We surveyed recent literature from animal experiments and clinical reports in the databases of PubMed and Elsevier ScienceDirect to analyze ionic mechanisms underlying ischemic cell damage and suggest promising ideas for stroke therapy...
October 17, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29044608/nutrient-sensing-in-pancreatic-islets-lessons-from-congenital-hyperinsulinism-and-monogenic-diabetes
#19
REVIEW
Ming Lu, Changhong Li
Pancreatic beta cells sense changes in nutrients during the cycles of fasting and feeding and release insulin accordingly to maintain glucose homeostasis. Abnormal beta cell nutrient sensing resulting from gene mutations leads to hypoglycemia or diabetes. Glucokinase (GCK) plays a key role in beta cell glucose sensing. As one form of congenital hyperinsulinism (CHI), activating mutations of GCK result in a decreased threshold for glucose-stimulated insulin secretion and hypoglycemia. In contrast, inactivating mutations of GCK result in diabetes, including a mild form (MODY2) and a severe form (permanent neonatal diabetes mellitus (PNDM))...
October 16, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29044528/endomorphins-potentiate-asic-currents-and-enhance-the-lactic-acid-mediated-increase-in-arterial-blood-pressure-effects-amplified-in-hindlimb-ischemia
#20
Mohamed Farrag, Julie K Drobish, Henry L Puhl, Joyce S Kim, Paul B Herold, Marc P Kaufman, Victor Ruiz-Velasco
Chronic muscle ischemia leads to accumulation of lactic acid and other inflammatory mediators with a subsequent drop in interstitial pH. Acid-sensing ion channels (ASICs), expressed in thin muscle afferents, sense the decrease in pH and evoke a pressor reflex known to increase mean arterial pressure. The naturally occurring endomorphins are also released by primary afferents under ischemic conditions. We examined whether high affinity mu opioid receptor (MOR) agonists, endomorphin-1 (E-1) and -2 (E-2), modulate ASIC currents and the lactic acid-mediated pressor reflex...
October 16, 2017: Journal of Physiology
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