ArticleThe Journal of physiology2005
Characterization of a proton-activated, outwardly rectifying anion channel.
Article in The Journal of physiology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 97 citations in OpenAlex.
- Proton-activated chloride channel 1 is essential for innate host defense against bacterial sepsis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- PAC regulates endo-, and exocytosis, and lysosomal-mitochondrial stress signaling in human mast cells.Cell communication and signaling : CCS · 2026Article
- Disentangling the mechanistic role of loop-C capping in Cys-loop receptor activation.Nature communications · 2025Article
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- Molecular insights into the inhibition of proton-activated chloride channel by transfer RNA.Cell research · 2024Article
- The plasma membrane inner leaflet PI(4,5)PNature communications · 2024Article
- Functional expression of the proton sensors ASIC1a, TMEM206, and OGR1 together with BKPflugers Archiv : European journal of physiology · 2024Article
- Physiological Functions of the Volume-Regulated Anion Channel VRAC/LRRC8 and the Proton-Activated Chloride Channel ASOR/TMEM206.Handbook of experimental pharmacology · 2024Article
- CBA (4-chloro-2-(2-chlorophenoxy)acetamido) benzoic acid) inhibits TMEM206 mediated currents and TMEM206 does not contribute to acid-induced cell death in colorectal cancer cells.Frontiers in pharmacology · 2024Article
- A new polymodal gating model of the proton-activated chloride channel.PLoS biology · 2023Article
- Review
- Identification of the Acid-Sensitive Site Critical for Chloral Hydrate (CH) Activation of the Proton-Activated Chloride Channel.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Molecular mechanism underlying desensitization of the proton-activated chloride channel PAC.eLife · 2022Article
- Probing effects of the SARS-CoV-2 E protein on membrane curvature and intracellular calcium.Biochimica et biophysica acta. Biomembranes · 2022Article
- Structural motifs for subtype-specific pH-sensitive gating of vertebrate otopetrin proton channels.eLife · 2022Article
- Molecular determinants of pH sensing in the proton-activated chloride channel.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Proton-gated anion transport governs macropinosome shrinkage.Nature cell biology · 2022Article
- Gating choreography and mechanism of the human proton-activated chloride channel ASOR.Science advances · 2022Article
- Clues and new evidences in arterial hypertension: unmasking the role of the chloride anion.Pflugers Archiv : European journal of physiology · 2022Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anion channels are present in every mammalian cell and serve many different functions, including cell volume regulation, ion transport across epithelia, regulation of membrane potential and vesicular acidification. Here we characterize a proton-activated, outwardly rectifying current endogenously expressed in HEK293 cells. Binding of three to four protons activated the anion permeable channels at external pH below 5.5 (50% activation at pH 5.1). The proton-activated current is strongly outwardly rectifying, due to an outwardly rectifying single channel conductance and an additional voltage dependent facilitation at depolarized membrane potentials. The anion channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS) rapidly and potently inhibited the channel (IC50: 2.9 microm). Flufenamic acid blocked this channel only slowly, while mibefradil and amiloride at high concentrations had no effect. As determined from reversal potential measurements under bi-ionic conditions, the relative permeability sequence of this channel was SCN-> I-> NO3-> Br-> Cl-. None of the previously characterized anion channel matches the properties of the proton-activated, outwardly rectifying channel. Specifically, the proton-activated and the volume-regulated anion channels are two distinct and separable populations of ion channels, each having its own set of biophysical and pharmacological properties. We also demonstrate endogenous proton-activated currents in primary cultured hippocampal astrocytes. The proton-activated current in astrocytes is also carried by anions, strongly outwardly rectifying, voltage dependent and inhibited by DIDS. Proton-activated, outwardly rectifying anion channels therefore may be a broadly expressed part of the anionic channel repertoire of mammalian cells.
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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.