ArticleThe Journal of biological chemistry2015
Protonation of the human PIEZO1 ion channel stabilizes inactivation.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 62 citations in OpenAlex.
- Piezo1 in Peripheral and Central Sensitisation: Implications for Chronic Pain.Bioengineering (Basel, Switzerland) · 2026Review
- Dual role of lactate in ferroptosis: Mechanisms, pathophysiology and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Piezo1 Channel Activators Yoda1 and Yoda2 in the Context of Red Blood Cells.Biomolecules · 2025Article
- PIEZO2 Proton Affinity and Availability May Also Regulate Mechanical Pain Sensitivity, Drive Central Sensitization and Neurodegeneration.International journal of molecular sciences · 2025Review
- Mechanosensitive Piezo1 channel: an emerging target in demyelination disease.Frontiers in cellular neuroscience · 2025Review
- Article
- Acid-base homeostasis orchestrated by NHE1 defines the pancreatic stellate cell phenotype in pancreatic cancer.JCI insight · 2023Article
- Mechanisms of PIEZO Channel Inactivation.International journal of molecular sciences · 2023Review
- Mechanical properties of the brain: Focus on the essential role of Piezo1-mediated mechanotransduction in the CNS.Brain and behavior · 2023Review
- The Janus-faced role of Piezo1 in cardiovascular health under mechanical stimulation.Genes & diseases · 2023Review
- Cooperativity in regulation of membrane protein function: phenomenological analysis of the effects of pH and phospholipids.Biophysical reviews · 2023Review
- Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Microscopic mechanism of PIEZO1 activation by pressure-induced membrane stretch.The Journal of general physiology · 2023Article
- The Role of the Piezo1 Mechanosensitive Channel in the Musculoskeletal System.International journal of molecular sciences · 2023Review
- The Impact of Plasma Membrane Ion Channels on Bone Remodeling in Response to Mechanical Stress, Oxidative Imbalance, and Acidosis.Antioxidants (Basel, Switzerland) · 2023Review
- Mechanotransductive receptorFrontiers in molecular biosciences · 2023Review
- CaInternational journal of molecular sciences · 2022Review
- Purinergic signaling is essential for full Psickle activation by hypoxia and by normoxic acid pH in mature human sickle red cells and in vitro-differentiated cultured human sickle reticulocytes.Pflugers Archiv : European journal of physiology · 2022Article
- Calcium-Permeable Channels in Tumor Vascularization: Peculiar Sensors of Microenvironmental Chemical and Physical Cues.Reviews of physiology, biochemistry and pharmacology · 2022Review
- A bibliometric analysis and review of recent researches on Piezo (2010-2020).Channels (Austin, Tex.) · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
PIEZO1 is a recently cloned eukaryotic cation-selective channel that opens with mechanical force. We found that extracellular protonation inhibits channel activation by ≈90% by increased occupancy in the closed or the inactivated state. Titration between pH 6.3 and 8.3 exhibited a pK of ≈6.9. The steepness of the titration data suggests positive cooperativity, implying the involvement of at least two protonation sites. Whole-cell recordings yielded results similar to patches, and pH 6.5 reduced whole-cell currents by >80%. The effects were reversible. To assess whether pH acts on the open or the inactivated state, we tested a double-mutant PIEZO1 that does not inactivate. Cell-attached patches and whole-cell currents from this mutant channel were pH-insensitive. Thus, protonation appears to be associated with domain(s) of the channel involved with inactivation. pH also did not affect mutant channels with point mutations at position 2456 that are known to exhibit slow inactivation. To determine whether the physical properties of the membrane are altered by pH and thereby affect channel gating, we measured patch capacitance during mechanical stimuli at pH 6.5 and 7.3. The rate constants for changes in patch capacitance were independent of pH, suggesting that bilayer mechanics are not involved. In summary, low pH stabilizes the inactivated state. This effect may be important when channels are activated under pathological conditions in which the pH is reduced, such as during ischemia.
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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.