Acid-sensing ion channels (ASICs) have been implicated in pain, and neurological and psychiatric disease. Wemmie et al. provide an update on the roles of ASICs in health and disease, and consider the implications for therapy and future lines of research.
#2Di Shi Liu(SJTU: Shanghai Jiao Tong University)H-Index: 5
Last. Tian Le Xu(SJTU: Shanghai Jiao Tong University)H-Index: 21
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Acid-sensing ion channels (ASICs) are proton-gated cation channels widely expressed in the peripheral and CNSs, which critically contribute to a variety of pathophysiological conditions that involve tissue acidosis, such as ischemic stroke and epileptic seizures. However, the trafficking mechanisms of ASICs and the related proteins remain largely unknown. Here, we demonstrate that ASIC1a, the main ASIC subunit in the brain, undergoes constitutive endocytosis in a clathrin-and dynamin-dependentma...
Last. Tian Le Xu(SJTU: Shanghai Jiao Tong University)H-Index: 21
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Tissue acidosis and inflammatory mediators play critical roles in inflammatory pain. Extracellular acidosis activates acid-sensing ion channels (ASICs), which have emerged as key sensors for extracellular protons in the central and peripheral nervous systems and play key roles in pain sensation and transmission. Additionally, inflammatory mediators, such as serotonin (5-HT), are known to enhance pain sensation. However, functional interactions among protons, inflammatory mediators, and ASICs in ...
Last. Cheng-Chang Lien(NYMU: National Yang-Ming University)H-Index: 20
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Acid-sensing ion channel-1a (ASIC1a) is localized in brain regions with high synaptic density and is thought to contribute to synaptic plasticity, learning, and memory. A prominent hypothesis is that activation of postsynaptic ASICs promotes depolarization, thereby augmenting N -methyl-d-aspartate receptor function and contributing to the induction of long-term potentiation (LTP). However, evidence for activation of postsynaptic ASICs during neurotransmission has not been established. Here, we r...
#1Xiang-ming Zha(USA: University of South Alabama)H-Index: 20
Extracellular acidification occurs in the brain with elevated neural activity, increased metabolism, and neuronal injury. This reduction in pH can have profound effects on brain function because pH regulates essentially every single biochemical reaction. Therefore, it is not surprising to see that Nature evolves a family of proteins, the acid-sensing ion channels (ASICs), to sense extracellular pH reduction. ASICs are proton-gated cation channels that are mainly expressed in the nervous system. ...
Neurodegeneration is the main cause for permanent disability in multiple sclerosis. The effect of current immunomodulatory treatments on neurodegeneration is insufficient. Therefore, direct neuroprotection and myeloprotection remain an important therapeutic goal. Targeting acid-sensing ion channel 1 (encoded by the ASIC1 gene), which contributes to the excessive intracellular accumulation of injurious Na(+) and Ca(2+) and is over-expressed in acute multiple sclerosis lesions, appears to be a via...
A new class of peptides, mambalgins, is isolated from the African snake the black mamba, which can abolish pain through inhibition of particular subtypes of acid-sensing ion channels expressed either in central or peripheral neurons.
#1Thomas W. Sherwood(The Ohio State University Wexner Medical Center)H-Index: 9
#2Erin Frey(The Ohio State University Wexner Medical Center)H-Index: 8
Last. Candice C. Askwith(The Ohio State University Wexner Medical Center)H-Index: 34
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The acid-sensing ion channels (ASICs) are a family of proton-sensing channels expressed throughout the nervous system. Their activity is linked to a variety of complex behaviors including fear, anxiety, pain, depression, learning, and memory. ASICs have also been implicated in neuronal degeneration accompanying ischemia and multiple sclerosis. As a whole, ASICs represent novel therapeutic targets for several clinically important disorders. An understanding of the correlation between ASIC structu...
#2Simon Akerman(UCSF: University of California, San Francisco)H-Index: 11
Last. Peter J. Goadsby(UCSF: University of California, San Francisco)H-Index: 137
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Objective: Migraine with aura is a severe debilitating neurological disorder with few relatively specific therapeutic options. Methods: We used amiloride, a blocker of epithelial sodium channels, to evaluate its pharmacological potential and explored the biology of a potential mechanism of action in well-established experimental models. Results: Amiloride was shown to block cortical spreading depression, the experimental correlate of aura, and inhibited trigeminal activation in in vivo migraine ...
Last. Emmanuel Deval(CNRS: Centre national de la recherche scientifique)H-Index: 21
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In rodent sensory neurons, acid-sensing ion channel 3 (ASIC3) has recently emerged as a particularly important sensor of nonadaptive pain associated with tissue acidosis. However, little is known about the human ASIC3 channel, which includes three splice variants differing in their C-terminal domain (hASIC3a, hASIC3b, and hASIC3c). hASIC3a transcripts represent the main mRNAs expressed in both peripheral and central neuronal tissues (dorsal root ganglia [DRG], spinal cord, and brain), where a sm...
#2Eric Lingueglia(University of Nice Sophia Antipolis)H-Index: 37
Last. Michel Lazdunski(University of Nice Sophia Antipolis)H-Index: 143
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A slight mechanical pressure applied to healthy skin results in blood vessel dilation, preserving blood flow. Defects in this vasodilatory response lead to an increased risk of pressure ulcers. Fromy et al. identify the neuronal mechanosensor that mediates this response in both rodents and humans: the ion channel Asic3.
#2Jay S. Naik(UNM: University of New Mexico)H-Index: 16
Last. Thomas C. Resta(UNM: University of New Mexico)H-Index: 31
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Pulmonary hypertension is characterized by sustained vasoconstriction and remodelling of the small pulmonary arteries, which is associated with persistent depolarization of the resting membrane potential (Em ) of pulmonary arterial smooth muscle cells (PASMCs). It is well-known that the underlying mechanism of this depolarization includes inhibition of K+ channels; however, whether other ion channels contribute to this depolarization is unknown. We previously reported that acid-sensing ion chann...
Last. Stephan A. Pless(UCPH: University of Copenhagen)H-Index: 19
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Acid-sensing ion channels (ASICs) are trimeric proton-gated cation channels involved in fast synaptic transmission. Pharmacological inhibition of ASIC1a reduces neurotoxicity and stroke infarct volumes, with the cysteine knot toxin Psalmotoxin-1 (PcTx1) being one of the most potent and selective inhibitors. PcTx1 binds at the subunit interface in the extracellular domain (ECD), but the mechanism and the conformational consequences of the interaction, as well as the number of toxin molecules requ...
Last. Emmanuel Deval(CNRS: Centre national de la recherche scientifique)H-Index: 21
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Dorsal horn of the spinal cord is an important crossroad of pain neuraxis, especially for the neuronal plasticity mechanisms that can lead to chronic pain states. Windup is a well-known spinal pain facilitation process initially described several decades ago, but which exact mechanism is still not fully understood. Here, we combine both ex vivo and in vivo electrophysiological recordings of spinal neurons with computational modelling to demonstrate a role for ASIC1a-containing channels in the wi...
#1Matthew L. Rook(URMC: University of Rochester Medical Center)H-Index: 1
#2Megan Miaro(U of O: University of Ottawa)H-Index: 1
Last. David M. MacLean(URMC: University of Rochester Medical Center)H-Index: 16
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Desensitization is a common feature of ligand-gated ion channels, although the molecular cause varies widely between channel types. Mutations that greatly reduce or nearly abolish desensitization have been described for many ligand-gated ion channels, including glutamate, GABA, glycine, and nicotinic receptors, but not for acid-sensing ion channels (ASICs) until recently. Mutating Gln276 to a glycine (Q276G) in human ASIC1a was reported to mostly abolish desensitization at both the macroscopic a...
Last. Tiandong Leng(Morehouse School of Medicine)H-Index: 13
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Oxidative stress is intimately tied to neurodegenerative diseases, including Parkinson’s disease and amyotrophic lateral sclerosis, and acute injuries, such as ischemic stroke and traumatic brain injury. Acid sensing ion channel 1a (ASIC1a), a proton-gated ion channel, has been shown to be involved in the pathogenesis of these diseases. However, whether oxidative stress affects the expression of ASIC1a remains elusive. In the current study, we examined the effect of hydrogen peroxide (H2O2), a m...
#2Kyle D. Berger(URMC: University of Rochester Medical Center)H-Index: 3
Last. David M. MacLean(URMC: University of Rochester Medical Center)H-Index: 16
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Acid-sensing ion channels (ASICs) are trimeric cation-selective channels activated by decreases in extracellular pH. The intracellular N and C terminal tails of ASIC1 influence channel gating, trafficking, and signaling in ischemic cell death. Despite several X-ray and cryo-EM structures of the extracellular and transmembrane segments of ASIC1, these important intracellular tails remain unresolved. Here, we describe the coarse topography of the chicken ASIC1 intracellular domains determined by f...
Last. Feihu Chen(Anhui Medical University)H-Index: 4
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Synovial hyperplasia, a profound alteration in the structure of synovial tissue, is the basis for cumulative joint destruction in rheumatoid arthritis (RA). It is generally accepted that controlling synovial hyperplasia can delay the progression of RA. As one of the most intensively studied isoforms of acid-sensing ion channels (ASICs), ASIC1a contributes to various physiopathologic conditions, including RA, due to its unique property of being permeable to Ca2+. However, the role and the regulat...
