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Flipping the Photoswitch: Ion Channels Under Light Control

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Novel Chemical Tools to Study Ion Channel Biology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 869))

Abstract

Nature has incorporated small photochromic molecules, colloquially termed ‘photoswitches’, in photoreceptor proteins to sense optical cues in phototaxis and vision. While Nature’s ability to employ light-responsive functionalities has long been recognized, it was not until recently that scientists designed, synthesized and applied synthetic photochromes to manipulate many of which open rapidly and locally in their native cell types, biological processes with the temporal and spatial resolution of light. Ion channels in particular have come to the forefront of proteins that can be put under the designer control of synthetic photochromes. Photochromic ion channel controllers are comprised of three classes, photochromic soluble ligands (PCLs), photochromic tethered ligands (PTLs) and photochromic crosslinkers (PXs), and in each class ion channel functionality is controlled through reversible changes in photochrome structure. By acting as light-dependent ion channel agonists, antagonist or modulators, photochromic controllers effectively converted a wide range of ion channels, including voltage-gated ion channels, ‘leak channels’, tri-, tetra- and pentameric ligand-gated ion channels, and temperature-sensitive ion channels, into man-made photoreceptors. Control by photochromes can be reversible, unlike in the case of ‘caged’ compounds, and non-invasive with high spatial precision, unlike pharmacology and electrical manipulation. Here, we introduce design principles of emerging photochromic molecules that act on ion channels and discuss the impact that these molecules are beginning to have on ion channel biophysics and neuronal physiology.

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References

  • Aldoshin SM (1990) Spiropyrans: structural features and photochemical properties. Russ Chem Rev 59:663–684

    Article  Google Scholar 

  • Banghart M, Borges K, Isacoff E, Trauner D, Kramer RH (2004) Light-activated ion channels for remote control of neuronal firing. Nat Neurosci 7(12):1381–1386

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Banghart MR, Mourot A, Fortin DL, Yao JZ, Kramer RH, Trauner D (2009) Photochromic blockers of voltage-gated potassium channels. Angew Chem Int Ed Engl 48(48):9097–9101. doi:10.1002/anie.200904504

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bartels E, Wassermann NH, Erlanger BF (1971) Photochromic activators of the acetylcholine receptor. Proc Natl Acad Sci U S A 68(8):1820–1823

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Beharry AA, Woolley GA (2011) Azobenzene photoswitches for biomolecules. Chem Soc Rev 40(8):4422–4437. doi:10.1039/c1cs15023e

    Article  CAS  PubMed  Google Scholar 

  • Berkovic G, Krongauz V, Weiss V (2000) Spiropyrans and spirooxazines for memories and switches. Chem Rev 100(5):1741–1754

    Article  CAS  PubMed  Google Scholar 

  • Bieth J, Vratsanos SM, Wassermann N, Erlanger BF (1969) Photoregulation of biological activity by photocromic reagents. II. Inhibitors of acetylcholinesterase. Proc Natl Acad Sci U S A 64(3):1103–1106

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Binshtok AM, Bean BP, Woolf CJ (2007) Inhibition of nociceptors by TRPV1-mediated entry of impermeant sodium channel blockers. Nature 449(7162):607–610. doi:10.1038/nature06191

    Article  CAS  PubMed  Google Scholar 

  • Browne LE, Nunes JP, Sim JA, Chudasama V, Bragg L, Caddick S, Alan North R (2014) Optical control of trimeric P2X receptors and acid-sensing ion channels. Proc Natl Acad Sci U S A 111(1):521–526. doi:10.1073/pnas.1318582111

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Caporale N, Kolstad KD, Lee T, Tochitsky I, Dalkara D, Trauner D, Kramer R, Dan Y, Isacoff EY, Flannery JG (2011) LiGluR restores visual responses in rodent models of inherited blindness. Mol Ther 19(7):1212–1219. doi:10.1038/mt.2011.103

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chabala LD, Lester HA (1986) Activation of acetylcholine receptor channels by covalently bound agonists in cultured rat myoballs. J Physiol 379:83–108

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chabala LD, Gurney AM, Lester HA (1985) Photoactivation and dissociation of agonist molecules at the nicotinic acetylcholine receptor in voltage-clamped rat myoballs. Biophys J 48(2):241–246. doi:10.1016/S0006-3495(85)83777-2

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chambers JJ, Banghart MR, Trauner D, Kramer RH (2006) Light-induced depolarization of neurons using a modified Shaker K(+) channel and a molecular photoswitch. J Neurophysiol 96(5):2792–2796

    Article  CAS  PubMed  Google Scholar 

  • Chen X, Islamova NI, Robles RV, Lees WJ (2011) Photochromic properties of a water-soluble methyl carboxylic acid indolylfulgimide. Photochem Photobiol Sci 10(6):1023–1029. doi:10.1039/c1pp05016h

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cordes T, Heinz B, Regner N, Hoppmann C, Schrader TE, Summerer W, Ruck-Braun K, Zinth W (2007) Photochemical Z–>E isomerization of a hemithioindigo/hemistilbene omega-amino acid. Chemphyschem 8(11):1713–1721

    Article  CAS  PubMed  Google Scholar 

  • Deal WJ, Erlanger BF, Nachmansohn D (1969) Photoregulation of biological activity by photochromic reagents. 3. Photoregulation of bioelectricity by acetylcholine receptor inhibitors. Proc Natl Acad Sci U S A 64(4):1230–1234

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dynamic Studies in Biology: phototriggers, Photoswitches and Caged Biomolecules (2005) Wiley-VCH. ISBN 3-527-30783-4

    Google Scholar 

  • Eggers K, Fyles TM, Montoya-Pelaez PJ (2001) Synthesis and characterization of photoswitchable lipids containing hemithioindigo chromophores. J Org Chem 66(9):2966–2977

    Article  CAS  PubMed  Google Scholar 

  • Fasold H, Klappenberger J, Meyer C, Remold H (1971) Bifunctional reagents for the crosslinking of proteins. Angew Chem Int Ed Engl 10(11):795–801

    Article  PubMed  Google Scholar 

  • Fehrentz T, Kuttruff CA, Huber FM, Kienzler MA, Mayer P, Trauner D (2012) Exploring the pharmacology and action spectra of photochromic open-channel blockers. Chembiochem 13(12):1746–1749. doi:10.1002/cbic.201200216

    Article  CAS  PubMed  Google Scholar 

  • Fortin DL, Dunn TW, Fedorchak A, Allen D, Montpetit R, Banghart MR, Trauner D, Adelman JP, Kramer RH (2011) Optogenetic photochemical control of designer K + channels in mammalian neurons. J Neurophysiol 106(1):488–496. doi:jn.00251.2011 [pii]10.1152/jn.00251.2011

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fritzsche J (1867) Note sur les carbures d’hydrogène solides, tirés du gaudron de houille. Compt Rend Acad Sci 69:1035–1037

    Google Scholar 

  • Fujimoto K, Kajino M, Sakaguchi I, Inouye M (2012) Photoswitchable, DNA-binding helical peptides assembled with two independently designed sequences for photoregulation and DNA recognition. Chemistry 18(32):9834–9840. doi:10.1002/chem.201201431

    Article  CAS  PubMed  Google Scholar 

  • Herre S, Steinle W, Rück-Braun K (2005) Synthesis of photoswitchable hemithioindigo-based w-amino acids and application in Boc-based peptide assembly. Synthesis 19:3297–3300

    Google Scholar 

  • Hirshberg Y (1950) Photochromie dans la serie de la bianthrone. Compt Rend Acad Sci 231(18):903–904

    Google Scholar 

  • Irie M (2000) Diarylethenes for memories and switches. Chem Rev 100(5):1685–1716

    Article  CAS  PubMed  Google Scholar 

  • Izquierdo-Serra M, Trauner D, Llobet A, Gorostiza P (2013) Optical control of calcium-regulated exocytosis. Biochim Biophys Acta 1830(3):2853–2860. doi:10.1016/j.bbagen.2012.11.003

    Article  CAS  PubMed  Google Scholar 

  • Janovjak H, Szobota S, Wyart C, Trauner D, Isacoff EY (2010) A light-gated, potassium-selective glutamate receptor for the optical inhibition of neuronal firing. Nat Neurosci 13(8):1027–1032

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Janovjak H, Sandoz G, Isacoff EY (2011) A modern ionotropic glutamate receptor with a K(+) selectivity signature sequence. Nat Commun 2:232. doi:10.1038/ncomms1231

    Article  CAS  PubMed  Google Scholar 

  • Ji TH (1983) Bifunctional reagents. Methods Enzymol 91:580–609

    Article  CAS  PubMed  Google Scholar 

  • Kienzler MA, Reiner A, Trautman E, Yoo S, Trauner D, Isacoff EY (2013) A red-shifted, fast-relaxing azobenzene photoswitch for visible light control of an ionotropic glutamate receptor. J Am Chem Soc 135(47):17683–17686. doi:10.1021/ja408104w

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kokel D, Cheung CY, Mills R, Coutinho-Budd J, Huang L, Setola V, Sprague J, Jin S, Jin YN, Huang XP, Bruni G, Woolf CJ, Roth BL, Hamblin MR, Zylka MJ, Milan DJ, Peterson RT (2013) Photochemical activation of TRPA1 channels in neurons and animals. Nat Chem Biol 9(4):257–263

    Google Scholar 

  • Kumita JR, Smart OS, Woolley GA (2000) Photo-control of helix content in a short peptide. Proc Natl Acad Sci U S A 97(8):3803–3808

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lemoine D, Habermacher C, Martz A, Mery PF, Bouquier N, Diverchy F, Taly A, Rassendren F, Specht A, Grutter T (2013) Optical control of an ion channel gate. Proc Natl Acad Sci U S A 110(51):20813–20818. doi:10.1073/pnas.1318715110

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lester HA, Krouse ME, Nass MM, Wassermann NH, Erlanger BF (1979) Light-activated drug confirms a mechanism of ion channel blockade. Nature 280(5722):509–510

    Article  CAS  PubMed  Google Scholar 

  • Lester HA, Krouse ME, Nass MM, Wassermann NH, Erlanger BF (1980) A covalently bound photoisomerizable agonist: comparison with reversibly bound agonists at Electrophorus electroplaques. J Gen Physiol 75(2):207–232

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Levitz J, Pantoja C, Gaub B, Janovjak H, Reiner A, Hoagland A, Schoppik D, Kane B, Stawski P, Schier AF, Trauner D, Isacoff EY (2013) Optical control of metabotropic glutamate receptors. Nat Neurosci 16(4):507–516. doi:10.1038/nn.3346

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Li D, Herault K, Isacoff EY, Oheim M, Ropert N (2012) Optogenetic activation of LiGluR-expressing astrocytes evokes anion channel-mediated glutamate release. J Physiol 590 (4):855–873. doi:10.1113/jphysiol.2011.219345

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mao S, Benninger RK, Yan Y, Petchprayoon C, Jackson D, Easley CJ, Piston DW, Marriott G (2008) Optical lock-in detection of FRET using synthetic and genetically encoded optical switches. Biophys J 94(11):4515–4524. doi:10.1529/biophysj.107.124859

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Marriott G, Mao S, Sakata T, Ran J, Jackson DK, Petchprayoon C, Gomez TJ, Warp E, Tulyathan O, Aaron HL, Isacoff EY, Yan Y (2008) Optical lock-in detection imaging microscopy for contrast-enhanced imaging in living cells. Proc Natl Acad Sci U S A 105(46):17789–17794

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mayer ML (2011) Structure and mechanism of glutamate receptor ion channel assembly, activation and modulation. Curr Opin Neurobiol 21(2):283–290. doi:10.1016/j.conb.2011.02.001

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mostoslavskii MA, Kravchenko MD (1970) Absorption spectra of 3-oxo-2,3-dihydrothionaphthene and its derivatives. Chem Heterocycl Comp 4:45–47

    Article  Google Scholar 

  • Mourot A, Kienzler MA, Banghart MR, Fehrentz T, Huber FM, Stein M, Kramer RH, Trauner D (2011) Tuning photochromic ion channel blockers. ACS Chem Neurosci 2(9):536–543. doi:10.1021/cn200037p

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mourot A, Fehrentz T, Feuvre Y L, Smith CM, Herold C, Dalkara D, Nagy F, Trauner D, Kramer RH (2012) Rapid optical control of nociception with an ion-channel photoswitch. Nat Methods 9(4):396–402. doi:10.1038/nmeth.1897

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nargeot J, Lester HA, Birdsall NJ, Stockton J, Wassermann NH, Erlanger BF (1982) A photoisomerizable muscarinic antagonist. Studies of binding and of conductance relaxations in frog heart. J Gen Physiol 79(4):657–678

    Article  CAS  PubMed  Google Scholar 

  • Numano R, Szobota S, Lau AY, Gorostiza P, Volgraf M, Roux B, Trauner D, Isacoff EY (2009) Nanosculpting reversed wavelength sensitivity into a photoswitchable iGluR. Proc Natl Acad Sci USA 106(16):6814–6819

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Petchprayoon C, Yan Y, Mao S, Marriott G (2011) Rational design, synthesis, and characterization of highly fluorescent optical switches for high-contrast optical lock-in detection (OLID) imaging microscopy in living cells. Bioorg Med Chem 19(3):1030–1040. doi:10.1016/j.bmc.2010.07.015

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Polosukhina A, Litt J, Tochitsky I, Nemargut J, Sychev Y, De Kouchkovsky I, Huang T, Borges K, Trauner D, Van Gelder RN, Kramer RH (2012) Photochemical restoration of visual responses in blind mice. Neuron 75(2):271–282. doi:10.1016/j.neuron.2012.05.022

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rau H (1973) Spectroscopic properties of organic azo compounds. Angew Chem Int Ed Engl 12:224–235

    Article  Google Scholar 

  • Regner N, Herzog TT, Haiser K, Hoppmann C, Beyermann M, Sauermann J, Engelhard M, Cordes T, Ruck-Braun K, Zinth W (2012) Light-switchable hemithioindigo-hemistilbene-containing peptides: ultrafast spectroscopy of the Z –> E isomerization of the chromophore and the structural dynamics of the peptide moiety. J Phys Chem B 116(14):4181–4191. doi:10.1021/jp300982a

    Article  CAS  PubMed  Google Scholar 

  • Reiter A, Skerra A, Trauner D, Schiefner A (2013) A photoswitchable neurotransmitter analogue bound to its receptor. BioChemistry 52(50):8972–8974. doi:10.1021/bi4014402

    Article  CAS  PubMed  Google Scholar 

  • Ridge KD, Palczewski K (2007) Visual rhodopsin sees the light: structure and mechanism of G protein signaling. J Biol Chem 282(13):9297–9301

    Article  CAS  PubMed  Google Scholar 

  • Rizzini L, Favory JJ, Cloix C, Faggionato D, O'Hara A, Kaiserli E, Baumeister R, Schafer E, Nagy F, Jenkins GI, Ulm R (2011) Perception of UV-B by the Arabidopsis UVR8 protein. Science 332(6025):103–106. doi:10.1126/science.1200660

    Article  CAS  PubMed  Google Scholar 

  • Rockwell NC, Lagarias JC (2006) The structure of phytochrome: a picture is worth a thousand spectra. Plant Cell 18(1):4–14

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Samanta S, Woolley GA (2011) Bis-azobenzene crosslinkers for photocontrol of peptide structure. Chembiochem 12(11):1712–1723. doi:10.1002/cbic.201100204

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sandoz G, Levitz J, Kramer RH, Isacoff EY (2012) Optical control of endogenous proteins with a photoswitchable conditional subunit reveals a role for TREK1 in GABA(B) signaling. Neuron 74(6):1005–1014. doi:10.1016/j.neuron.2012.04.026

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Standaert RF, Park SB (2006) Abc amino acids: design, synthesis, and properties of new photoelastic amino acids. J Org Chem 71(21):7952–7966

    Article  CAS  PubMed  Google Scholar 

  • Stawski P, Sumser M, Trauner D (2012) A photochromic agonist of AMPA receptors. Angew Chem Int Ed Engl 51(23):5748–5751. doi:10.1002/anie.201109265

    Article  CAS  PubMed  Google Scholar 

  • Stein M, Middendorp SJ, Carta V, Pejo E, Raines DE, Forman SA, Sigel E, Trauner D (2012) Azo-propofols: photochromic potentiators of GABA(A) receptors. Angew Chem Int Ed Engl 51(42):10500–10504. doi:10.1002/anie.201205475

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Szobota S, Gorostiza P, Del Bene F, Wyart C, Fortin DL, Kolstad KD, Tulyathan O, Volgraf M, Numano R, Aaron HL, Scott EK, Kramer RH, Flannery J, Baier H, Trauner D, Isacoff EY (2007) Remote control of neuronal activity with a light-gated glutamate receptor. Neuron 54(4):535–545

    Article  CAS  PubMed  Google Scholar 

  • Tochitsky I, Banghart MR, Mourot A, Yao JZ, Gaub B, Kramer RH, Trauner D (2012) Optochemical control of genetically engineered neuronal nicotinic acetylcholine receptors. Nat Chem 4(2):105–111. doi:10.1038/nchem.1234

    Article  CAS  PubMed  Google Scholar 

  • Tochitsky I, Polosukhina A, Degtyar VE, Gallerani N, Smith CM, Friedman A, Van Gelder RN, Trauner D, Kaufer D, Kramer RH (2014) Restoring visual function to blind mice with a photoswitch that exploits electrophysiological remodeling of retinal ganglion cells. Neuron 81(4):800–813. doi:10.1016/j.neuron.2014.01.003

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Volgraf M, Gorostiza P, Numano R, Kramer RH, Isacoff EY, Trauner D (2006) Allosteric control of an ionotropic glutamate receptor with an optical switch. Nat Chem Biol 2(1):47–52

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Volgraf M, Gorostiza P, Szobota S, Helix MR, Isacoff EY, Trauner D (2007) Reversibly caged glutamate: a photochromic agonist of ionotropic glutamate receptors. J Am Chem Soc 129(2):260–261. doi:10.1021/ja067269o

    Article  CAS  PubMed  Google Scholar 

  • Wyart C, Bene FD, Warp E, Scott EK, Trauner D, Baier H, Isacoff EY (2009) Optogenetic dissection of a behavioural module in the vertebrate spinal cord. Nature 461(7262):407–410

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yokoyama Y (2000) Fulgides for memories and switches. Chem Rev 100(5):1717–1740

    Article  CAS  PubMed  Google Scholar 

  • Yue L, Pawlowski M, Dellal SS, Xie A, Feng F, Otis TS, Bruzik KS, Qian H, Pepperberg DR (2012) Robust photoregulation of GABA(A) receptors by allosteric modulation with a propofol analogue. Nat Commun 3:1095. doi:10.1038/ncomms2094

    Article  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Science and Technology Austria, Am Campus 1, A-3400, Klosterneuburg, Austria

    Catherine K. McKenzie, Inmaculada Sanchez-Romero & Harald Janovjak

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  1. Catherine K. McKenzie
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  2. Inmaculada Sanchez-Romero
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  3. Harald Janovjak
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Correspondence to Harald Janovjak .

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Editors and Affiliations

  1. Molecular Physiology and Biophysics, University of Iowa, IOWA CITY, Iowa, USA

    Christopher Ahern

  2. Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark

    Stephan Pless

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McKenzie, C., Sanchez-Romero, I., Janovjak, H. (2015). Flipping the Photoswitch: Ion Channels Under Light Control. In: Ahern, C., Pless, S. (eds) Novel Chemical Tools to Study Ion Channel Biology. Advances in Experimental Medicine and Biology, vol 869. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2845-3_6

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