ArticleThe Journal of biological chemistry2016
Modulation of Acid-sensing Ion Channel 1a by Intracellular pH and Its Role in Ischemic Stroke.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Acid-sensing ion channels in ischemic stroke: amplifying and constraining neuronal injury in a phase-specific framework.Pflugers Archiv : European journal of physiology · 2026Review
- ASIC1a Promotes nucleus pulposus derived stem cells apoptosis through modulation of SIRT3-dependent mitochondrial redox homeostasis in intervertebral disc degeneration.Redox report : communications in free radical research · 2025Article
- Association between base excess and mortality in critically ill patients with ischemic stroke: a retrospective cohort study.BMC neurology · 2024Article
- Article
- Acid-sensing ion channels and downstream signalling in cancer cells: is there a mechanistic link?Pflugers Archiv : European journal of physiology · 2024Review
- Expression, Functional Polymorphism, and Diagnostic Values of MIAT rs2331291 and H19 rs217727 Long Non-Coding RNAs in Cerebral Ischemic Stroke Egyptian Patients.International journal of molecular sciences · 2024Article
- Identification and analgesic activity study of analgesic protein Ⅶ-2 fromThe journal of venomous animals and toxins including tropical diseases · 2024Article
- Acidosis induces synovial fibroblasts to release vascular endothelial growth factor via acid-sensitive ion channel 1a.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Commentary: Large Acid-Evoked Currents, Mediated by ASIC1a, Accompany Differentiation in Human Dopaminergic Neurons.Frontiers in cellular neuroscience · 2021Article
- Emerging immune and cell death mechanisms in stroke: Saponins as therapeutic candidates.Brain, behavior, & immunity - health · 2020Review
- Protein Kinase C Regulates ASIC1a Protein Expression and Channel Function via NF-kB Signaling Pathway.Molecular neurobiology · 2020Article
- [Acid-sensing ion channels differentially affect ictal-like and non-ictal-like epileptic activities of mouse hippocampal pyramidal neurons in acidotic extracellular pH].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2020Article
- SLC9A4 in the organum vasculosum of the lamina terminalis is a [NaPflugers Archiv : European journal of physiology · 2020Article
- Factors and Molecular Mechanisms Influencing the Protein Synthesis, Degradation and Membrane Trafficking of ASIC1a.Frontiers in cell and developmental biology · 2020Review
- Going the Extra (Synaptic) Mile: Excitotoxicity as the Road Toward Neurodegenerative Diseases.Frontiers in cellular neuroscience · 2020Review
- Article
- Acute Ethanol Exposure Promotes Autophagy-Lysosome Pathway-Dependent ASIC1a Protein Degradation and Protects Against Acidosis-Induced Neurotoxicity.Molecular neurobiology · 2019Article
- Acid-sensing ion channel 1a is involved in ischaemia/reperfusion induced kidney injury by increasing renal epithelia cell apoptosis.Journal of cellular and molecular medicine · 2019Article
- Pesticides as the drivers of neuropsychotic diseases, cancers, and teratogenicity among agro-workers as well as general public.Environmental science and pollution research international · 2019Review
- Danger-Associated Molecular Patterns (DAMPs): the Derivatives and Triggers of Inflammation.Current allergy and asthma reports · 2018Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
An important contributor to brain ischemia is known to be extracellular acidosis, which activates acid-sensing ion channels (ASICs), a family of proton-gated sodium channels. Lines of evidence suggest that targeting ASICs may lead to novel therapeutic strategies for stroke. Investigations of the role of ASICs in ischemic brain injury have naturally focused on the role of extracellular pH in ASIC activation. By contrast, intracellular pH (pHi) has received little attention. This is a significant gap in our understanding because the ASIC response to extracellular pH is modulated by pHi, and activation of ASICs by extracellular protons is paradoxically enhanced by intracellular alkalosis. Our previous studies show that acidosis-induced cell injury in in vitro models is attenuated by intracellular acidification. However, whether pHi affects ischemic brain injury in vivo is completely unknown. Furthermore, whereas ASICs in native neurons are composed of different subunits characterized by distinct electrophysiological/pharmacological properties, the subunit-dependent modulation of ASIC activity by pHi has not been investigated. Using a combination of in vitro and in vivo ischemic brain injury models, electrophysiological, biochemical, and molecular biological approaches, we show that the intracellular alkalizing agent quinine potentiates, whereas the intracellular acidifying agent propionate inhibits, oxygen-glucose deprivation-induced cell injury in vitro and brain ischemia-induced infarct volume in vivo Moreover, we find that the potentiation of ASICs by quinine depends on the presence of the ASIC1a, ASIC2a subunits, but not ASIC1b, ASIC3 subunits. Furthermore, we have determined the amino acids in ASIC1a that are involved in the modulation of ASICs by pHi.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.