ArticleProceedings of the National Academy of Sciences of the United States of America2012
Human ASIC3 channel dynamically adapts its activity to sense the extracellular pH in both acidic and alkaline directions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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55 citing papers in PubMed, 87 citations in OpenAlex.
- Acid Sensing Ion Channels (ASICs) in the brain: emerging roles in physiology and pathology.Pflugers Archiv : European journal of physiology · 2026Review
- The Potential and Prospects of Marine Drugs in Intervening Nerve-Tumor Crosstalk.Marine drugs · 2026Review
- Electric field stimulation-responsive hydrogels for bone regeneration: from mechanisms to applications.Bone research · 2026Review
- Signaling pathways and ion channels in osteoarthritis: a review of recent advances.Frontiers in immunology · 2026Review
- Molecular mechanisms and hotspots of pH sensing in ASIC1a revealed by computational and functional analysis.Communications biology · 2025Article
- ASIC currents in cultured primate retinal amacrine/ganglion cells.Physiological reports · 2025Article
- Classical Models of Hydroxide for Proton Hopping Simulations.The journal of physical chemistry. B · 2024Article
- Acid-sensing ion channel 3 is a new potential therapeutic target for the control of glioblastoma cancer stem cells growth.Scientific reports · 2024Article
- Ion channels in osteoarthritis: emerging roles and potential targets.Nature reviews. Rheumatology · 2024Review
- Acid-sensing ion channels and downstream signalling in cancer cells: is there a mechanistic link?Pflugers Archiv : European journal of physiology · 2024Review
- 4-(Azolyl)-Benzamidines as a Novel Chemotype for ASIC1a Inhibitors.International journal of molecular sciences · 2024Article
- Functional characterization of acid-sensing ion channels in the cerebellum-originating medulloblastoma cell line DAOY and in cerebellar granule neurons.Pflugers Archiv : European journal of physiology · 2023Article
- Gene therapy for chronic pain: emerging opportunities in target-rich peripheral nociceptors.Nature reviews. Neuroscience · 2023Review
- Involvement of Potassium Channel Signalling in Migraine Pathophysiology.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Review
- Pathology and physiology of acid‑sensitive ion channels in the digestive system (Review).International journal of molecular medicine · 2022Review
- Acid-Sensing Ion Channel 2: Function and Modulation.Membranes · 2022Review
- Distribution of acid-sensing ion channel subunits in human sensory neurons contrasts with that in rodents.Brain communications · 2022Article
- Acid-sensing ion channel 3: An analgesic target.Channels (Austin, Tex.) · 2021Review
- Acid-Sensing Ion Channels and Mechanosensation.International journal of molecular sciences · 2021Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 small proportion of hASIC3c transcripts is also detected. We show that hASIC3 channels (hASIC3a, hASIC3b, or hASIC3c) are able to directly sense extracellular pH changes not only during acidification (up to pH 5.0), but also during alkalization (up to pH 8.0), an original and inducible property yet unknown. When the external pH decreases, hASIC3 display a transient acid mode with brief activation that is relevant to the classical ASIC currents, as previously described. On the other hand, an external pH increase activates a sustained alkaline mode leading to a constitutive activity at resting pH. Both modes are inhibited by the APETx2 toxin, an ASIC3-type channel inhibitor. The alkaline sensitivity of hASIC3 is an intrinsic property of the channel, which is supported by the extracellular loop and involves two arginines (R68 and R83) only present in the human clone. hASIC3 is thus able to sense the extracellular pH in both directions and therefore to dynamically adapt its activity between pH 5.0 and 8.0, a property likely to participate in the fine tuning of neuronal membrane potential and to neuron sensitization in various pH environments.
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