Abstract
The development of photochromic and photoswitchable ligands for ion channels and receptors has made important contributions to optopharmacology and optogenetic pharmacology. These compounds provide new tools to study ion channel proteins and to understand their function and pathological implications. Here, we describe the design, operation, and applications of the available photoswitches, with special emphasis on ligand- and voltage-gated channels.
Antoni Bautista-Barrufet and Mercè Izquierdo-Serra contributed equally to this work
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Alivisatos AP, Chun M, Church GM, Deisseroth K, Donoghue JP, Greenspan RJ, McEuen PL, Roukes ML, Sejnowski TJ, Weiss PS, Yuste R (2013) Neuroscience. The brain activity map. Science 339:1284–1285
Gorostiza P, Isacoff EY (2008) Optical switches for remote and noninvasive control of cell signaling. Science 322:395–399
Tye KM, Deisseroth K (2012) Optogenetic investigation of neural circuits underlying brain disease in animal models. Nat Rev Neurosci 13:251–266
Gorostiza P, Isacoff E (2007) Optical switches and triggers for the manipulation of ion channels and pores. Mol BioSyst 3:686–704
Kramer RH, Mourot A, Adesnik H (2013) Optogenetic pharmacology for control of native neuronal signaling proteins. Nat Neurosci 16:816–823
Gorostiza P, Isacoff EY (2008) Nanoengineering ion channels for optical control. Physiology (Bethesda) 23:238–247
Szobota S, Isacoff EY (2010) Optical control of neuronal activity. Annu Rev Biophys 39:329–348
Szobota S, McKenzie C, Janovjak H (2013) Optical control of ligand-gated ion channels. Methods Mol Biol 998:417–435
Mourot A, Fehrentz T, Kramer RH (2013) Photochromic potassium channel blockers: design and electrophysiological characterization. Methods Mol Biol 995:89–105
Connolly CN, Wafford KA (2004) The Cys-loop superfamily of ligand-gated ion channels: the impact of receptor structure on function. Biochem Soc Trans 32:529–534
Ortells MO, Lunt GG (1995) Evolutionary history of the ligand-gated ion-channel superfamily of receptors. Trends Neurosci 18:121–127
Hilf RJ, Dutzler R (2009) A prokaryotic perspective on pentameric ligand-gated ion channel structure. Curr Opin Struct Biol 19:418–424
Brejc K, van Dijk WJ, Klaassen RV, Schuurmans M, van der Oost J, Smit AB, Sixma TK (2001) Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors. Nature 411:269–276
Changeux JP, Edelstein SJ (1998) Allosteric receptors after 30 years. Neuron 21:959–980
Yip GM, Chen ZW, Edge CJ, Smith EH, Dickinson R, Hohenester E, Townsend RR, Fuchs K, Sieghart W, Evers AS, Franks NP (2013) A propofol binding site on mammalian GABAA receptors identified by photolabeling. Nat Chem Biol 9:715–720
Hille B (2001) Ion channels of excitable membranes. Sinauer Associates, Inc., Sunderland
Bartels E, Wassermann NH, Erlanger BF (1971) Photochromic activators of the acetylcholine receptor. Proc Natl Acad Sci USA 68:1820–1823
Silman I, Karlin A (1969) Acetylcholine receptor: covalent attachment of depolarizing groups at the active site. Science 164:1420–1421
Chabala LD, Lester HA (1986) Activation of acetylcholine receptor channels by covalently bound agonists in cultured rat myoballs. J Physiol 379:83–108
Lester HA, Chang HW (1977) Response of acetylcholine receptors to rapid photochemically produced increases in agonist concentration. Nature 266:373–374
Barrantes FJ (1980) Modulation of acethylcholine receptor states by thiol modification. Biochemistry 19:2957–2965
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 4:105–111
Chow BY, Han X, Dobry AS, Qian X, Chuong AS, Li M, Henninger MA, Belfort GM, Lin Y, Monahan PE, Boyden ES (2010) High-performance genetically targetable optical neural silencing by light-driven proton pumps. Nature 463:98–102
Zhang F, Wang LP, Brauner M, Liewald JF, Kay K, Watzke N, Wood PG, Bamberg E, Nagel G, Gottschalk A, Deisseroth K (2007) Multimodal fast optical interrogation of neural circuitry. Nature 446:633–639
Kasparov S, Herlitze S (2013) Optogenetics at a crossroads? Exp Physiol 98:971–972
Raster P, Späth A, Bultakova S, Gorostiza P, König B, Bregestovski P (2013) New GABA amides activating GABAA receptors. Beilstein J Org Chem 9:406–410
Stein M, Middendorp SJ, Carta V, Pejo E, Raines DE, Forman SA, Sigel E, Trauner D (2012) Azo-propofols: photochromic potentiators of GABAA receptors. Angew Chem Int Ed Engl 51:10500–10504
Yue L, Pawlowski M, Dellal SS, Xie A, Feng F, Otis TS, Bruzik KS, Qian H, Pepperberg DR (2012) Robust photoregulation of GABAA receptors by allosteric modulation with a propofol analogue. Nat Commun 3:1095
Stein M, Breit A, Fehrentz T, Gudermann T, Trauner D (2013) Optical control of TRPV1 channels. Angew Chem Int Ed Engl 52:9845–9848
Gereau RW, Swanson GT (2008) The glutamate receptors. Humana Press, New York
Traynelis SF, Wollmuth LP, McBain CJ, Menniti FS, Vance KM, Ogden KK, Hansen KB, Yuan H, Myers SJ, Dingledine R (2010) Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev 62:405–496
Felder CB, Graul RC, Lee AY, Merkle HP, Sadee W (1999) The Venus flytrap of periplasmic binding proteins: an ancient protein module present in multiple drug receptors. AAPS PharmSci 1:E2
Sobolevsky AI, Rosconi MP, Gouaux E (2009) X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor. Nature 462:745–756
Doumazane E, Scholler P, Fabre L, Zwier JM, Trinquet E, Pin JP, Rondard P (2013) Illuminating the activation mechanisms and allosteric properties of metabotropic glutamate receptors. Proc Natl Acad Sci USA 110:1416–1425
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 2:47–52
Gorostiza P, Volgraf M, Numano R, Szobota S, Trauner D, Isacoff EY (2007) Mechanisms of photoswitch conjugation and light activation of an ionotropic glutamate receptor. Proc Natl Acad Sci USA 104:10865–10870
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 135:17683–17686
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 129:260–261
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 106:6814–6819
Reiter A, Skerra A, Trauner D, Schiefner A (2013) A photoswitchable neurotransmitter analogue bound to its receptor. Biochemistry 52:8972–8974
Stawski P, Sumser M, Trauner D (2012) A photochromic agonist of AMPA receptors. Angew Chem Int Ed Engl 51:5748–5751
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 13:1027–1032
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 16:507–516
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 54:535–545
Wyart C, del Bene F, Warp E, Scott EK, Trauner D, Baier H, Isacoff EY (2009) Optogenetic dissection of a behavioural module in the vertebrate spinal cord. Nature 461:407–410
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 590:855–873
Izquierdo-Serra M, Trauner D, Llobet A, Gorostiza P (2013) Optical control of calcium-regulated exocytosis. Biochim Et Biophys Acta-Gen Subj 1830:2853–2860
Izquierdo-Serra M, Trauner D, Llobet A, Gorostiza P (2013) Optical modulation of neurotransmission using calcium photocurrents through the ion channel LiGluR. Front Mol Neurosci 6:1–8
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 19:1212–1219
Izquierdo-Serra M, Gascón-Moya M, Hirtz JJ, Pittolo S, Poskanzer KE, Ferrer E, Alibés E, Busqué F, Yuste R, Hernando J, Gorostiza P (2014) Two-photon neuronal and astrocytic stimulation with azobenzene-based photoswitches. J Am Chem Soc (Accepted Manuscript)
Abrams ZR, Warrier A, Wang Y, Trauner D, Zhang X (2012) Tunable oscillations in the Purkinje neuron. Phys Rev E: Stat Nonlin Soft Matter Phys 85:041905
Kawate T, Michel JC, Birdsong WT, Gouaux E (2009) Crystal structure of the ATP-gated P2X(4) ion channel in the closed state. Nature 460:592–598
Conley EC (1996) The ion channel facts book I: extracellular ligand-gated ion channels. Academic Press Limited, London
Valera S, Hussy N, Evans RJ, Adami N, North RA, Surprenant A, Buell G (1994) A new class of ligand-gated ion channel defined by P2X receptor for extracellular ATP. Nature 371:516–519
Lima SQ, Miesenböck G (2005) Remote control of behavior through genetically targeted photostimulation of neurons. Cell 121:141–152
Zemelman BV, Nesnas N, Lee GA, Miesenbock G (2003) Photochemical gating of heterologous ion channels: remote control over genetically designated populations of neurons. Proc Natl Acad Sci USA 100:1352–1357
Zemelman BV, Lee GA, Ng M, Miesenböck G (2002) Selective photostimulation of genetically ChARGed neurons. Neuron 33:15–22
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 USA 111:521–526
Lemoine D, Habermacher C, Martz A, Méry 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 USA 110:20813–20818
Banghart M, Borges K, Isacoff E, Trauner D, Kramer RH (2004) Light-activated ion channels for remote control of neuronal firing. Nat Neurosci 7:1381–1386
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 96:2792–2796
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 106:488–496
Fortin DL, Banghart MR, Dunn TW, Borges K, Wagenaar DA, Gaudry Q, Karakossian MH, Otis TS, Kristan WB, Trauner D, Kramer RH (2008) Photochemical control of endogenous ion channels and cellular excitability. Nat Methods 5:331–338
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 48:9097–9101
Mourot A, Fehrentz T, le Feuvre Y, 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 9:396–402
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 2:536–543
Fehrentz T, Kuttruff CA, Huber FM, Kienzler MA, Mayer P, Trauner D (2012) Exploring the pharmacology and action spectra of photochromic open-channel blockers. Chem Bio Chem 13:1746–1749
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 75:271–282
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 GABAB signaling. Neuron 74:1005–1014
Venkatachalam K, Montell C (2007) TRP channels. Annu Rev Biochem 76:387–417
Papagiakoumou E, Begue A, Leshem B, Schwartz O, Stell BM, Bradley J, Oron D, Emiliani V (2013) Functional patterned multiphoton excitation deep inside scattering tissue. Nat Photon 7:274–278
Denk W, Strickler JH, Webb WW (1990) Two-photon laser scanning fluorescence microscopy. Science 248:73–76
Oron D, Papagiakoumou E, Anselmi F, Emiliani V (2012) Two-photon optogenetics. Prog Brain Res 196:119–143
Watson BO, Nikolenko V, Yuste R (2009) Two-photon imaging with diffractive optical elements. Front Neural Circ 3:6
Szymanski W, Beierle JM, Kistemaker HAV, Velema WA, Feringa BL (2013) Reversible photocontrol of biological systems by the incorporation of molecular photoswitches. Chem Rev 113:6114–6178
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Bautista-Barrufet, A., Izquierdo-Serra, M., Gorostiza, P. (2014). Photoswitchable Ion Channels and Receptors. In: Benfenati, F., Di Fabrizio, E., Torre, V. (eds) Novel Approaches for Single Molecule Activation and Detection. Advances in Atom and Single Molecule Machines. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-43367-6_9
Download citation
DOI: https://doi.org/10.1007/978-3-662-43367-6_9
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-662-43366-9
Online ISBN: 978-3-662-43367-6
eBook Packages: Chemistry and Materials ScienceChemistry and Material Science (R0)