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TRPswitch-A Step-Function Chemo-optogenetic Ligand for the Vertebrate TRPA1 Channel
Pui-Ying Lam1, Aditya R Thawani2, Enrique Balderas3
1Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, United States.
Journal of the American Chemical Society
|September 23, 2020
Summary
We discovered TRPswitch, a novel chemo-optogenetic tool for controlling cell activity. This system enables precise, reversible light-induced switching of the TRPA1 channel, offering a powerful new method for optical control.
Area of Science:
- Optogenetics
- Channelrhodopsins
- Molecular biology
Background:
- Current chemo-optogenetic tools have limitations like low conductance and inability to control both on/off switching.
- Transient Receptor Potential ankyrin 1 (TRPA1) channels are ideal targets due to high unitary conductance.
Purpose of the Study:
- To discover novel photoswitchable ligands for TRPA1 channels.
- To develop a chemo-optogenetic system with improved control and efficiency.
Main Methods:
- Zebrafish behavior-based screening to identify TRPswitch scaffold.
- Molecular determinant elucidation for TRPswitch optimization.
- Demonstration in larval zebrafish hearts expressing Trpa1b.
Main Results:
- TRPswitch enables reversible, repeatable, and quantitative light-induced activation/deactivation of TRPA1.
- Violet and green light control TRPA1 channel activity (on/off switching).
- Heartbeat control in zebrafish demonstrated using TRPswitch and light.
Conclusions:
- TRPA1/TRPswitch is a novel chemo-optogenetic system with high conductance, efficiency, and bidirectional optical switching.
- This system is applicable for large depolarization currents and sustained channel activation.
- Offers a powerful tool for optical control of cell activity in various biological systems.
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