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Chemical Neurobiology

Volume 995 of the series Methods in Molecular Biology pp 89-105

Date:

Photochromic Potassium Channel Blockers: Design and Electrophysiological Characterization

  • Alexandre MourotAffiliated withDepartment of Molecular and Cellular Biology, University of California Berkeley Email author 
  • , Timm FehrentzAffiliated withDepartment of Chemistry, Ludwig-Maximillians-Universität-University of MunichDepartment of Pharmacology, Ludwig-Maximillians-Universität-University of MunichCenter for Integrated Protein Science, Ludwig-Maximillians-Universität-University of MunichDepartment of Molecular and Cellular Biology, University of California Berkeley
  • , Richard H. KramerAffiliated withDepartment of Molecular and Cellular Biology, University of California Berkeley

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Abstract

Voltage-gated potassium (K v) channels are membrane proteins that open a selective pore upon membrane depolarization, allowing K+ ions to flow down their electrochemical gradient. In neurons, K v channels play a key role in repolarizing the membrane potential during the falling phase of the action potential, often resulting in an after hyperpolarization. Opening of K v channels results in a decrease of cellular excitability, whereas closing (or pharmacological block) has the opposite effect, increased excitability. We have developed a series of photosensitive blockers for K v channels that enable reversible, optical regulation of potassium ion flow. Such molecules can be used for remote control of neuronal excitability using light as an on/off switch. Here we describe the design and electrophysiological characterization of photochromic blockers of ion channels. Our focus is on K v channels but in principle, the techniques described here can be applied to other ion channels and signaling proteins.

Key words

Azobenzene Photoswitch Photochromic ligand Ion channel Photopharmacology Quaternary ammonium compounds Electrophysiology