ArticleThe Journal of general physiology2010
Function of the HVCN1 proton channel in airway epithelia and a naturally occurring mutation, M91T.
Article in The Journal of general physiology, 2010. 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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Who cites it
55 citing papers in PubMed, 85 citations in OpenAlex.
- Modulators of the Human Voltage-Gated Proton Channel HPharmaceuticals (Basel, Switzerland) · 2025Review
- Zinc inhibits the voltage-gated proton channel HCNL1.Biophysical journal · 2024Article
- Transcendent Aspects of Proton Channels.Annual review of physiology · 2024Review
- Role of the Voltage-Gated Proton Channel Hv1 in Nervous Systems.Neuroscience bulletin · 2023Review
- Unexpected expansion of the voltage-gated proton channel family.The FEBS journal · 2023Article
- N-terminal region is responsible for mHv1 channel activity in MDSCs.Frontiers in pharmacology · 2023Article
- Role of voltage-gated proton channel (Hv1) in cancer biology.Frontiers in pharmacology · 2023Review
- Multiple mechanisms contribute to fluorometry signals from the voltage-gated proton channel.Communications biology · 2022Article
- RNA-Seq Analyses Reveal Roles of the HVCN1 Proton Channel in Cardiac pH Homeostasis.Frontiers in cell and developmental biology · 2022Article
- Large pH oscillations promote host defense against human airways infection.The Journal of experimental medicine · 2021Article
- Airway Surface Liquid pH Regulation in Airway Epithelium Current Understandings and Gaps in Knowledge.International journal of molecular sciences · 2021Review
- Regulation of Neutrophil Functions by Hv1/VSOP Voltage-Gated Proton Channels.International journal of molecular sciences · 2021Review
- Functions and Mechanisms of the Voltage-Gated Proton Channel Hv1 in Brain and Spinal Cord Injury.Frontiers in cellular neuroscience · 2021Review
- Voltage and pH difference across the membrane control the S4 voltage-sensor motion of the Hv1 proton channel.Scientific reports · 2020Article
- Zinc modulation of proton currents in a new voltage-gated proton channel suggests a mechanism of inhibition.The FEBS journal · 2020Article
- Voltage-dependent structural models of the human Hv1 proton channel from long-timescale molecular dynamics simulations.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Proton channel blockers inhibit Duox activity independent of Hv1 effects.Redox biology · 2020Article
- Voltage-gated proton channels exist in the plasma membrane of human oocytes.Human reproduction (Oxford, England) · 2019Article
- Solute carrier family 9, subfamily A, member 3 (SLC9A3)/sodium-hydrogen exchanger member 3 (NHE3) dysregulation and dilated intercellular spaces in patients with eosinophilic esophagitis.The Journal of allergy and clinical immunology · 2018Article
- Voltage and pH sensing by the voltage-gated proton channel, HJournal of the Royal Society, Interface · 2018Review
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Authors and funding
3 authors.
Funding
Abstract
Airways secrete considerable amounts of acid. In this study, we investigated the identity and the pH-dependent function of the apical H(+) channel in the airway epithelium. In pH stat recordings of confluent JME airway epithelia in Ussing chambers, Zn-sensitive acid secretion was activated at a mucosal threshold pH of approximately 7, above which it increased pH-dependently at a rate of 339 +/- 34 nmol x h(-1) x cm(-2) per pH unit. Similarly, H(+) currents measured in JME cells in patch clamp recordings were readily blocked by Zn and activated by an alkaline outside pH. Small interfering RNA-mediated knockdown of HVCN1 mRNA expression in JME cells resulted in a loss of H(+) currents in patch clamp recordings. Cloning of the open reading frame of HVCN1 from primary human airway epithelia resulted in a wild-type clone and a clone characterized by two sequential base exchanges (452T>C and 453G>A) resulting in a novel missense mutation, M91T HVCN1. Out of 95 human genomic DNA samples that were tested, we found one HVCN1 allele that was heterozygous for the M91T mutation. The activation of acid secretion in epithelia that natively expressed M91T HVCN1 required approximately 0.5 pH units more alkaline mucosal pH values compared with wild-type epithelia. Similarly, activation of H(+) currents across recombinantly expressed M91T HVCN1 required significantly larger pH gradients compared with wild-type HVCN1. This study provides both functional and molecular indications that the HVCN1 H(+) channel mediates pH-regulated acid secretion by the airway epithelium. These data indicate that apical HVCN1 represents a mechanism to acidify an alkaline airway surface liquid.
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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.