Abstract
Photoswitchable blockers of potassium channels can be used to optically control neuronal excitability and hold great promise for vision restoration. Here, we report a series of improved photoswitchable blockers that are furnished with a new pharmacophore based on the local anesthetic bupivacaine. These azobupivacaines (ABs) enable optical control over the delayed rectifier channel K v 2.1. and target the two-pore domain potassium channel TREK-1. For the first time, we have identified a compound that blocks conductance in the dark and potentiates it upon illumination. Using light as a trigger, ABs efficiently and reversibly silence action potential firing of hippocampal neurons in acute mouse brain slices.
Original language | English (US) |
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Pages (from-to) | 2886-2891 |
Number of pages | 6 |
Journal | ACS Chemical Neuroscience |
Volume | 9 |
Issue number | 12 |
DOIs | |
State | Published - Dec 19 2018 |
Keywords
- Kv2.1
- Photochromic ligand
- TREK-1
- channel blocker
- local anesthetics
- photopharmacology
ASJC Scopus subject areas
- Biochemistry
- Physiology
- Cognitive Neuroscience
- Cell Biology