Irritant-evoked activation and calcium modulation of the TRPA1 receptor
@article{Zhao2020IrritantevokedAA, title={Irritant-evoked activation and calcium modulation of the TRPA1 receptor}, author={Jianhua Zhao and John V. Lin King and Candice E. Paulsen and Yifan Cheng and David Julius}, journal={Nature}, year={2020}, volume={585}, pages={141 - 145} }
The transient receptor potential ion channel TRPA1 is expressed by primary afferent nerve fibres, in which it functions as a low-threshold sensor for structurally diverse electrophilic irritants, including small volatile environmental toxicants and endogenous algogenic lipids 1 . TRPA1 is also a ‘receptor-operated’ channel whose activation downstream of metabotropic receptors elicits inflammatory pain or itch, making it an attractive target for novel analgesic therapies 2 . However, the…
44 Citations
Functional evidence of distinct electrophile-induced activation states of the ion channel TRPA1
- BiologyBiochemistry and biophysics reports
- 2021
Prerequisite Binding Modes Determine the Dynamics of Action of Covalent Agonists of Ion Channel TRPA1
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It was shown how reversible interactions with prerequisite binding sites contribute to structural changes of TRPA1 leading to covalent bonding of agonists, which allowed a mechanism-based forecast of new, druggable binding sites of potent agonists.
Atomistic mechanisms of human TRPA1 activation by electrophile irritants through molecular dynamics simulation and mutual information analysis
- Biology, ChemistryScientific reports
- 2022
The authors' simulations reveal that an open pore is structurally stable in the presence of open ‘pockets’ in the C621/C665 region, but rapidly collapses and closes when these pockets are shut, while molecules bound at C665 are shown to be able to rotate in and out of the pocket, allowing for immediate stabilisation of transient open states.
Mini-review: The nociceptive sensory functions of the polymodal receptor Transient Receptor Potential Ankyrin Type 1 (TRPA1)
- BiologyNeuroscience Letters
- 2021
Transient receptor potential ankyrin 1 and calcium: Interactions and association with disease (Review)
- BiologyExperimental and therapeutic medicine
- 2021
The therapeutic potential of the TRPA1 channel is highlighted, which is expected to become a novel direction for the prevention and treatment of health conditions such as cancer and neurodegenerative diseases.
Slack Potassium Channels Modulate TRPA1-Mediated Nociception in Sensory Neurons
- BiologyCells
- 2022
Patch-clamp recordings in sensory neurons and in a HEK cell line transfected with TRPA1 and Slack revealed that Slack-dependent potassium currents (IKS) are modulated in aTRPA1-dependent manner.
Transient receptor potential ankyrin 1 channel: An evolutionarily tuned thermosensor.
- BiologyPhysiological research
- 2021
This review aims at providing some of the recent knowledge on the molecular mechanisms underlying the temperature sensitivity of TRPA1, and demonstrates how the search for differences in temperature and chemical sensitivity between human and mouse TRPA 1 orthologues can be a useful approach to identifying important domains with a key role in channel activation.
Role of TRPA1 in Tissue Damage and Kidney Disease
- Biology, MedicineInternational journal of molecular sciences
- 2021
In in vivo animal studies, TRPA1 prevented sepsis-induced or Ang-II-induced and ischemia-reperfusion renal injury by maintaining mitochondrial haemostasis or via the downregulation of macrophage-mediated inflammation, respectively.
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