Optical Control of a Delayed Rectifier and a Two-Pore Potassium Channel with a Photoswitchable Bupivacaine

Philipp Leippe, Nils Winter, Martin P. Sumser, Dirk Trauner

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)2886-2891
Number of pages6
JournalACS Chemical Neuroscience
Volume9
Issue number12
DOIs
StatePublished - Dec 19 2018

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Keywords

  • Kv2.1
  • Photochromic ligand
  • TREK-1
  • channel blocker
  • local anesthetics
  • photopharmacology

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

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