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Tuning photochromic ion channel blockers.
Alexandre Mourot1, Michael A Kienzler, Matthew R Banghart
1Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
ACS Chemical Neuroscience
|August 4, 2012
Summary
New photochromic channel blockers offer convenient light-based control of neuronal activity. These visible-light-activated compounds self-deactivate in the dark, simplifying photopharmacological applications.
Area of Science:
- Neuroscience
- Chemical Biology
- Optogenetics
Background:
- Photochromic channel blockers offer light-inducible neuronal modulation.
- Existing azobenzene blockers require UV-A light and active wavelength switching.
Purpose of the Study:
- To develop novel photochromic channel blockers operating in the visible light spectrum.
- To create blockers with enhanced features like rapid dark-inactivation and automatic reversibility.
Main Methods:
- Synthesis of novel red-shifted azobenzene derivatives.
- Electrophysiological characterization of K(v) channel block and unblock kinetics.
- Assessment of photochromic properties under visible light and in dark conditions.
Main Results:
- Developed red-shifted azobenzene blockers functioning entirely within the visible spectrum.
- Demonstrated rapid self-inactivation in the dark for improved control.
- Engineered a variant switchable with blue light and automatically reverting to an inactive state.
Conclusions:
- Novel photochromic channel blockers enable efficient neuronal activity modulation using visible light.
- These compounds offer advantages in speed, ease of use, and automatic reversibility.
- Potential applications in photopharmacological control of neuronal circuits under mild conditions.
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