ArticleThe Journal of general physiology2016
The Hv1 proton channel responds to mechanical stimuli.
Article in The Journal of general physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Functional evidence of Hv1-mediated proton flux in cardiac mitochondria.Channels (Austin, Tex.) · 2026Article
- Article
- Interrogating the structure and function of the human voltage-gated proton channel (hHbioRxiv : the preprint server for biology · 2025Article
- Expression and Purification of the Human Voltage-Gated Proton Channel (hHBio-protocol · 2025Article
- A novel method for expressing and purifying large quantities of functional and stable human voltage-gated proton channel (hHProtein science : a publication of the Protein Society · 2025Article
- Interaction with stomatin directs human proton channels into cholesterol-dependent membrane domains.Biophysical journal · 2024Article
- Review
- The Emerging Role of Microglial Hv1 as a Target for Immunomodulation in Myelin Repair.Aging and disease · 2024Review
- Temperature Dependent Activity of the Voltage-Gated Proton Channel.Advances in experimental medicine and biology · 2024Review
- Mechanically-primed voltage-gated proton channels from angiosperm plants.Nature communications · 2023Article
- Mechanosensitive aquaporins.Biophysical reviews · 2023Review
- Article
- The HVCN1 voltage-gated proton channel contributes to pH regulation in canine ventricular myocytes.The Journal of physiology · 2022Article
- MRTF may be the missing link in a multiscale mechanobiology approach toward macrophage dysfunction in space.Frontiers in cell and developmental biology · 2022Article
- Anion and Cation Permeability of the Mouse TMEM16F Calcium-Activated Channel.International journal of molecular sciences · 2021Article
- Human induced pluripotent stem cell-derived atrial cardiomyocytes carrying an SCN5A mutation identify nitric oxide signaling as a mediator of atrial fibrillation.Stem cell reports · 2021Article
- Voltage-gated proton channels from fungi highlight role of peripheral regions in channel activation.Communications biology · 2021Article
- Pathogenic mutations perturb calmodulin regulation of NaBiochemical and biophysical research communications · 2020Article
- pH-Channeling in Cancer: How pH-Dependence of Cation Channels Shapes Cancer Pathophysiology.Cancers · 2020Review
- Voltage vs. Ligand I: Structural basis of the intrinsic flexibility of S3 segment and its significance in ion channel activation.Channels (Austin, Tex.) · 2019Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The voltage-gated proton channel, Hv1, is expressed in tissues throughout the body and plays important roles in pH homeostasis and regulation of NADPH oxidase. Hv1 operates in membrane compartments that experience strong mechanical forces under physiological or pathological conditions. In microglia, for example, Hv1 activity is potentiated by cell swelling and causes an increase in brain damage after stroke. The channel complex consists of two proton-permeable voltage-sensing domains (VSDs) linked by a cytoplasmic coiled-coil domain. Here, we report that these VSDs directly respond to mechanical stimuli. We find that membrane stretch facilitates Hv1 channel opening by increasing the rate of activation and shifting the steady-state activation curve to less depolarized potentials. In the presence of a transmembrane pH gradient, membrane stretch alone opens the channel without the need for strong depolarizations. The effect of membrane stretch persists for several minutes after the mechanical stimulus is turned off, suggesting that the channel switches to a "facilitated" mode in which opening occurs more readily and then slowly reverts to the normal mode observed in the absence of membrane stretch. Conductance simulations with a six-state model recapitulate all the features of the channel's response to mechanical stimulation. Hv1 mechanosensitivity thus provides a mechanistic link between channel activation in microglia and brain damage after stroke.
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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.