ArticleThe Journal of physiology2007
Sustained activation of proton channels and NADPH oxidase in human eosinophils and murine granulocytes requires PKC but not cPLA2 alpha activity.
Article in The Journal of physiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 67 citations in OpenAlex.
- Modulators of the Human Voltage-Gated Proton Channel HPharmaceuticals (Basel, Switzerland) · 2025Review
- Hv1 channel in immune cells and pharmacology.Pharmacological research · 2025Review
- The Role of Ion-Transporting Proteins on Crosstalk Between the Skeletal Muscle and Central Nervous Systems Elicited by Physical Exercise.Molecular neurobiology · 2025Review
- Molecular regulation of neutrophil swarming in health and disease: Lessons from the phagocyte oxidase.iScience · 2023Review
- Voltage-Gated Proton Channels in the Tree of Life.Biomolecules · 2023Review
- Role of voltage-gated proton channel (Hv1) in cancer biology.Frontiers in pharmacology · 2023Review
- A Review on the Role of Bicarbonate and Proton Transporters during Sperm Capacitation in Mammals.International journal of molecular sciences · 2022Review
- ORAI1 and ORAI2 modulate murine neutrophil calcium signaling, cellular activation, and host defense.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The voltage-gated proton channel hHv1 is functionally expressed in human chorion-derived mesenchymal stem cells.Scientific reports · 2020Article
- Article
- Voltage and pH sensing by the voltage-gated proton channel, HJournal of the Royal Society, Interface · 2018Review
- Extracellular phosphates enhance activities of voltage-gated proton channels and production of reactive oxygen species in murine osteoclast-like cells.Pflugers Archiv : European journal of physiology · 2017Article
- The inhibition of voltage-gated HPflugers Archiv : European journal of physiology · 2017Article
- Actions and Mechanisms of Polyunsaturated Fatty Acids on Voltage-Gated Ion Channels.Frontiers in physiology · 2017Review
- The Hv1 proton channel responds to mechanical stimuli.The Journal of general physiology · 2016Article
- The intimate and controversial relationship between voltage-gated proton channels and the phagocyte NADPH oxidase.Immunological reviews · 2016Review
- Insights into the structure and function of HV1 from a meta-analysis of mutation studies.The Journal of general physiology · 2016Review
- Effects of unsaturated fatty acids on the kinetics of voltage-gated proton channels heterologously expressed in cultured cells.The Journal of physiology · 2016Article
- Voltage-Gated Proton Channels as Novel Drug Targets: From NADPH Oxidase Regulation to Sperm Biology.Antioxidants & redox signaling · 2015Review
- The Voltage-Gated Proton Channel: A Riddle, Wrapped in a Mystery, inside an Enigma.Biochemistry · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The prevailing hypothesis that a signalling pathway involving cPLA(2)alpha is required to enhance the gating of the voltage-gated proton channel associated with NADPH oxidase was tested in human eosinophils and murine granulocytes. This hypothesis invokes arachidonic acid (AA) liberated by cPLA(2)alpha as a final activator of proton channels. In human eosinophils studied in the perforated-patch configuration, phorbol myristate acetate (PMA) stimulation elicited NADPH oxidase-generated electron current (I(e)) and enhanced proton channel gating identically in the presence or absence of three specific cPLA(2)alpha inhibitors, Wyeth-1, pyrrolidine-2 and AACOCF(3) (arachidonyl trifluoromethyl ketone). In contrast, PKC inhibitors GFX (GF109203X) or staurosporine prevented the activation of either proton channels or NADPH oxidase. PKC inhibition during the respiratory burst reversed the activation of both molecules, suggesting that ongoing phosphorylation is required. This effect of GFX was inhibited by okadaic acid, implicating phosphatases in proton channel deactivation. Proton channel activation by AA was partially reversed by GFX or staurosporine, indicating that AA effects are due in part to activation of PKC. In granulocytes from mice with the cPLA(2)alpha gene disrupted (knockout mice), PMA or fMetLeuPhe activated NADPH oxidase and proton channels in a manner indistinguishable from the responses of control cells. Thus, cPLA(2)alpha is not essential to activate the proton conductance or for a normal respiratory burst. Instead, phosphorylation of the proton channel or an activating molecule converts the channel to its activated gating mode. The existing paradigm for regulation of the concerted activity of proton channels and NADPH oxidase must be revised.
Indexed as
Identifiers
What OpenQuestion holds
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.