title: Photochromic potassium channel blockers: design and electrophysiological characterization.
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.
authors.affiliation: Department of Molecular and Cellular Biology, University of California Berkeley, Berkeley, CA, USA. almourot@gmail.com
authors.forename: Alexandre
authors.initials: A
authors.lastname: Mourot
authors.forename: Timm
authors.initials: T
authors.lastname: Fehrentz
authors.forename: Richard H
authors.initials: RH
authors.lastname: Kramer
mesh_terms: D000818:Animals; D001391:Azo Compounds / Q000737:chemistry* / Q000494:pharmacology / Q000528:radiation effects; D018929:Cell Culture Techniques; D015195:Drug Design; D057809:HEK293 Cells; D006801:Humans; D008027:Light; D008564:Membrane Potentials; D018408:Patch-Clamp Techniques / Q000379:methods; D055668:Photochemical Processes; D026902:Potassium Channel Blockers / Q000737:chemistry* / Q000494:pharmacology / Q000528:radiation effects; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051637:Shaker Superfamily of Potassium Channels / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013237:Stereoisomerism; D014162:Transfection
chemical_list: D001391:Azo Compounds; D026902:Potassium Channel Blockers; D011994:Recombinant Proteins; D051637:Shaker Superfamily of Potassium Channels