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Photochromic Potassium Channel Blockers: Design and Electrophysiological Characterization

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Chemical Neurobiology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 995))

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.

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Acknowledgments

We are grateful to Matthew R. Banghart (Harvard Medical School), Michael Kienzler, and Dirk Trauner (University of Munich) for the design and synthesis of PCLs described in this chapter, and to Christopher Davenport for helpful comments and suggestions.

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Authors and Affiliations

  1. Department of Molecular and Cellular Biology, University of California Berkeley, Berkeley, CA, USA

    Alexandre Mourot, Timm Fehrentz & Richard H. Kramer

  2. Department of Chemistry, Ludwig-Maximillians-Universität-University of Munich, Munich, Germany

    Timm Fehrentz

  3. Department of Pharmacology, Ludwig-Maximillians-Universität-University of Munich, Munich, Germany

    Timm Fehrentz

  4. Center for Integrated Protein Science, Ludwig-Maximillians-Universität-University of Munich, Munich, Germany

    Timm Fehrentz

Authors
  1. Alexandre Mourot
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  2. Timm Fehrentz
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  3. Richard H. Kramer
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Corresponding author

Correspondence to Alexandre Mourot .

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Editors and Affiliations

  1. , Department of Neurobiology, Harvard Medical School, Longwood Ave 220, Boston, 02115, Massachusetts, USA

    Matthew R. Banghart

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Mourot, A., Fehrentz, T., Kramer, R.H. (2013). Photochromic Potassium Channel Blockers: Design and Electrophysiological Characterization. In: Banghart, M. (eds) Chemical Neurobiology. Methods in Molecular Biology, vol 995. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-345-9_7

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  • DOI: https://doi.org/10.1007/978-1-62703-345-9_7

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-344-2

  • Online ISBN: 978-1-62703-345-9

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