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Characterizing Mammalian Zinc Transporters Using an In Vitro Zinc Transport Assay
Published on: June 2, 2023
Zinc activates damage-sensing TRPA1 ion channels
Hongzhen Hu1, Michael Bandell, Matt J Petrus
1Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, California 92121, USA.
Nature Chemical Biology
|February 10, 2009
Summary
Zinc excites pain-sensing neurons via TRPA1 channels, causing pain and inflammation. This study reveals TRPA1 as a key target for zinc
Area of Science:
- Neuroscience
- Cell Biology
- Trace Element Metabolism
Background:
- Zinc is an essential trace element vital for numerous proteins and cell signaling.
- High zinc concentrations can be cytotoxic, causing pain and inflammation via unknown pathways.
Purpose of the Study:
- To elucidate the mechanism by which excess zinc induces pain and inflammation.
- To identify the molecular targets responsible for zinc-induced nociception.
Main Methods:
- Investigated the role of the TRPA1 (transient receptor potential cation channel subfamily A member 1) channel in zinc-induced nociception in mice.
- Examined the activation mechanism of TRPA1 by zinc, including required intracellular residues and zinc influx.
Main Results:
- Zinc excites nociceptive somatosensory neurons and causes nociception in mice.
- Zinc activates TRPA1 through a novel mechanism requiring intracellular zinc influx and interaction with cysteine and histidine residues.
- TRPA1 exhibits high sensitivity to intracellular zinc, with activation occurring at low nanomolar concentrations.
Conclusions:
- TRPA1 is identified as a critical sensor for the sensory effects of zinc.
- These findings highlight TRPA1 as a significant target for managing zinc-related pain and inflammation.
- The study supports a developing understanding of zinc's role as a signaling molecule modulating sensory pathways.
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