ArticleProceedings of the National Academy of Sciences of the United States of America2009
Voltage-gated proton channels maintain pH in human neutrophils during phagocytosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 173 citations in OpenAlex.
- Differential antibacterial control by neutrophil subsets.Blood advances · 2018Trial
- Amyloid precursor protein is a subunit of microglial Hv1 channels.Current opinion in immunology · 2026Review
- Modulators of the Human Voltage-Gated Proton Channel HPharmaceuticals (Basel, Switzerland) · 2025Review
- Hv1 channel in immune cells and pharmacology.Pharmacological research · 2025Review
- Interaction with stomatin directs human proton channels into cholesterol-dependent membrane domains.Biophysical journal · 2024Article
- Honokiol alleviates monosodium urate-induced gouty pain by inhibiting voltage-gated proton channels in mice.Inflammopharmacology · 2024Article
- The Emerging Role of Microglial Hv1 as a Target for Immunomodulation in Myelin Repair.Aging and disease · 2024Review
- Transcendent Aspects of Proton Channels.Annual review of physiology · 2024Review
- Temperature Dependent Activity of the Voltage-Gated Proton Channel.Advances in experimental medicine and biology · 2024Review
- Role of the Voltage-Gated Proton Channel Hv1 in Nervous Systems.Neuroscience bulletin · 2023Review
- Voltage-Gated Proton Channels in the Tree of Life.Biomolecules · 2023Review
- Microglial reprogramming by Hv1 antagonism protects neurons from inflammatory and glutamate toxicity.Journal of neurochemistry · 2023Article
- The formation and function of the neutrophil phagosome.Immunological reviews · 2023Review
- Unexpected expansion of the voltage-gated proton channel family.The FEBS journal · 2023Article
- Role of voltage-gated proton channel (Hv1) in cancer biology.Frontiers in pharmacology · 2023Review
- Nematode homologs of the sour taste receptor Otopetrin1 are evolutionarily conserved acid-sensitive proton channels.Frontiers in cell and developmental biology · 2023Article
- Multiple mechanisms contribute to fluorometry signals from the voltage-gated proton channel.Communications biology · 2022Article
- Structural motifs for subtype-specific pH-sensitive gating of vertebrate otopetrin proton channels.eLife · 2022Article
- Role of the voltage-gated proton channel Hv1 in insulin secretion, glucose homeostasis, and obesity.Journal of physiology and biochemistry · 2022Review
- Inhibiting Hv1 channel in peripheral sensory neurons attenuates chronic inflammatory pain and opioid side effects.Cell research · 2022Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Phagocytosis of microbial invaders represents a fundamental defense mechanism of the innate immune system. The subsequent killing of microbes is initiated by the respiratory burst, in which nicotinamide adenine dinucleotide phosphate (NADPH) oxidase generates vast amounts of superoxide anion, precursor to bactericidal reactive oxygen species. Cytoplasmic pH regulation is crucial because NADPH oxidase functions optimally at neutral pH, yet produces enormous quantities of protons. We monitored pH(i) in individual human neutrophils during phagocytosis of opsonized zymosan, using confocal imaging of the pH sensing dye SNARF-1, enhanced by shifted excitation and emission ratioing, or SEER. Despite long-standing dogma that Na(+)/H(+) antiport regulates pH during the phagocyte respiratory burst, we show here that voltage-gated proton channels are the first transporter to respond. During the initial phagocytotic event, pH(i) decreased sharply, and recovery required both Na(+)/H(+) antiport and proton current. Inhibiting myeloperoxidase attenuated the acidification, suggesting that diffusion of HOCl into the cytosol comprises a substantial acid load. Inhibiting proton channels with Zn(2+) resulted in profound acidification to levels that inhibit NADPH oxidase. The pH changes accompanying phagocytosis in bone marrow phagocytes from HVCN1-deficient mice mirrored those in control mouse cells treated with Zn(2+). Both the rate and extent of acidification in HVCN1-deficient cells were twice larger than in control cells. In summary, acid extrusion by proton channels is essential to the production of reactive oxygen species during phagocytosis.
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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.