ФОТОХРОМНАЯ МОДУЛЯЦИЯ ЦИС-ПЕТЕЛЬНЫХ РЕЦЕПТОР-УПРАВЛЯЕМЫХ КАНАЛОВ
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Ключевые слова

фотофармакология
светоуправляемые молекулярные переключатели
никотиновые рецепторы ацетилхолина
ГАМК-рецепторы
глициновые рецепторы
синаптическая передача

Как цитировать

Брежестовский, П. Д., & Пономарева, Д. Н. (2021). ФОТОХРОМНАЯ МОДУЛЯЦИЯ ЦИС-ПЕТЕЛЬНЫХ РЕЦЕПТОР-УПРАВЛЯЕМЫХ КАНАЛОВ. Российский физиологический журнал им. И. М. Сеченова, 107(4-5), 436–457. https://doi.org/10.31857/S0869813921040051

Аннотация

Благодаря успехам молекулярной и клеточной биологии, развитию химического синтеза и современных технологий, экспериментальная база современных исследований обогатились новыми направлениями, в которых свет играет ключевую роль как инструмент модуляции функций организмов. Одним из них является фотофармакология – направление, в котором используются химически синтезируемые светоуправляемые соединения, способные контролировать функции биологических молекул. При освещении определёнными длинами световых волн эти фотохромные модуляторы переключаются между активной и неактивной формой и изменяют активность функционально важных белковых молекул — рецепторов, ионных каналов, ферментов и др. В данном обзоре кратко представлены соединения, модулирующие функции ионотропных Цис-петельных рецепторов ацетилхолина, ГАМК и глицина. Первым рецептор-управляемым каналом, для которого был открыт способ управления с помощью светоуправляемых молекул, является никотиновый рецептор ацетилхолина (нАХР). В 1970-х - 80-х годах были созданы блокаторы и активаторы нАХР, состоящие из азобензола (светоуправляемого переключателя) и агонистов. В нынешнем тысячелетии создано новое поколение соединений, обеспечивающих светоуправляемый контроль активностью нАХР. Прикрепляющиеся фотохромные лиганды состоят из малеимида для связывания с цистеиновыми группами аминокислот, фотопереключателя азобензола и лиганда для взаимодействия с рецептором. Новые фотохромы, избирательно активируют или блокируют мышечные и нейрональные рецепторы и являются перспективными для изучения физиологической роли нАХР в нервной системе. Для светоуправляемого контроля активностью ГАМК-рецепторов создана обширная библиотека фотохромных соединений. Некоторые из них модулируют активность, взаимодействуя с активным центром рецептора, другие являются светоуправляемыми блокаторами хлор-избирательных ионных каналов. Недавно создано также два первых фотохромных модулятора активности глициновых рецепторов. В целом, фотофармакология является перспективным направлением, открывающим уникальные возможности для дистанционного управления физиологическими функциями, а также исследования процессов торможения и возбуждения в нейронных сетях и моделях нейрональных патологий.

https://doi.org/10.31857/S0869813921040051
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Литература

Магазаник ЛГ (1968) Механизм десенситизации постсинаптической мембраны мышечных волокон. Биофизика 13(1): 199-202. [Magazanik LG (1968) On the mechanism of desensitization of the muscle fiber postsynaptic membrane. Biofizika 13(1): 199-202 (In Russ)].

Magazanik LG, Nasledov GA (1970) Desensitization to acetylcholine of frog tonic muscle fibres. Nature 226(5243): 370-371.

Magazanik LG, Vyskocit F (1975) The effect of temperature on desensitization kinetics at the post‐synaptic membrane of the frog muscle fibre. J Physiol 249(2): 285-300.

Magazanik LG, Snetkov VA, Giniatullin RA, Khazipov RN. (1990) Changes in the time course of miniature endplate currents induced by bath-applied acetylcholine. Neurosci Lett 113(3): 281-285.

Giniatullin RA, Magazanik LG (1998) Desensitization of the post-synaptic membrane of neuromuscular synapses induced by spontaneous quantum secretion of mediator. Neurosci Behav Physiol 28(4): 438-442.

Magazanik LG (1976) Functional properties of postjunctional membrane. Annu Rev Pharmacol Toxicol 16(1): 161-175.

Magazanik LG (2000) Blockade of ion channels as an approach to studying AMPA receptor subtypes. Neurosci Behav Physiol: 30(1): 27-35.

Тихонов ДБ, Магазаник ЛГ (2008) Происхождение и молекулярная эволюция ионотропных рецепторов глутaматa. Рос физиол журн им И.М. Сеченова 94(9): 989-1004. [Tikhonov DB, Magazanik LG (2008) Origin and molecular evolution of ionotropic glutamate receptors. Russ J Physiol 94(9): 989-1004 (In Russ)].

Калеменев СВ, Зубарева ОЕ, Лукомская НЯ, Магазаник ЛГ (2012) Нейропротекторное действие неконкурентных блокаторов NMDA-рецепторов ИЭМ-1957 и мемантина на модели фокальной ишемии мозга. Докл Акад наук 443 (6): 750-750. [Kalemenev SV, Zubareva OE, Lukomskaya NY, Magazanik LG (2012) Neuroprotective effect of noncompetitive NMDA receptor antagonists IEM-1957 and memantine in experimental focal cerebral ischemia. Dokl Biol Sci 443(1): 78-80 (In Russ)].

Ватаев СИ, Оганесян ГА, Лукомская НЯ, Магазаник ЛГ (2013) Влияние блокаторов каналов ионотропных глутаматных рецепторов на эффекты депривации сна у крыс. Рос физиол журн им И.М. Сеченова 99(5): 575-585. [Vataev SI, Oganesian GA, Lukomskaia N, Magazanik LG (2013) The action of ionotropic glutamate receptor channel blockers on effects of sleep deprivation in rats. Russ J Physiol 99(5): 575-585 (In Russ)].

Malkin SL, Kim KK, Tikhonov DB, Magazanik LG, Zaitsev AV (2015) Statistical models suggest presence of two distinct subpopulations of miniature EPSCs in fast-spiking interneurons of rat prefrontal cortex. Neuroscience 301: 508-519. https://doi.org/:10.1016/j.neuroscience.2015.06.034

Чижов АВ, Амахин ДВ, Зайцев АВ, Магазаник ЛГ (2018) AMPAR-опосредованные интериктальные разряды в нейронах энторинальной коры: эксперимент и модель. Докл Акад наук 479(1):103-106 [Chizhov AV, Amakhin DV, Zaizev AV, Magazanik LG (2018) AMPAR-mediated interictal discharges in neurons of entorhinal cortex: experiment and model. Dokl Biol Sci 479(1): 47-50 (In Russ)]. https://doi.org/:10.1134/S0012496618020011

Bregestovski P, Maleeva G, Gorostiza P (2018) Light‐induced regulation of ligand‐gated channel activity. Br J Pharmacol 175(11): 1892-1902. https://doi.org/:10.1111/bph.14022

Lin WC, Tsai MC., Rajappa R, Kramer RH (2018) Design of a highly bistable photoswitchable tethered ligand for rapid and sustained manipulation of neurotransmission. J Am Chem Soc 140(24): 7445-7448. https://doi.org/:10.1021/jacs.8b03942

Deisseroth K (2011) Optogenetics. Nat Methods 8(1): 26-29. https://doi.org/:10.1038/nmeth.f.324

Kim CK, Adhikari A, Deisseroth K (2017) Integration of optogenetics with complementary methodologies in systems neuroscience. Nat Rev Neurosci 18(4): 222-235. https://doi.org/:10.1038/nrn.2017.15

Gorostiza P, Isacoff EY (2008) Optical switches for remote and noninvasive control of cell signaling. Science 322(5900): 395-399. https://doi.org/:10.1126/science.1166022

Bregestovski P, Waseem T, Mukhtarov M. (2009) Genetically encoded optical sensors for monitoring of intracellular chloride and chloride-selective channel activity. Front Mol Neurosci 2(15). https://doi.org/:10.3389/neuro.02.015.2009

Suzuki J, Kanemaru K, Iino M. (2016) Genetically encoded fluorescent indicators for organellar calcium imaging. Biophys J 111(6): 1119-1131. https://doi.org/:10.1016/j.bpj.2016.04.054

Imamura H, Nhat KPH, Togawa H, Saito K, Iino R, Kato-Yamada Y, Nagai T, Noji H (2009) Visualization of ATP levels inside single living cells with fluorescence resonance energy transfer-based genetically encoded indicators. Proc Natl Acad Sci U S A. 106(37): 15651-15656. https://doi.org/:10.1073/pnas.0904764106

Berg J, Hung YP, Yellen G (2009) A genetically encoded fluorescent reporter of ATP: ADP ratio. Nat Methods 6(2): 161-166. https://doi.org/:10.1038/nmeth.1288

Schumacher CH, Körschen HG, Nicol C, Gasser C, Seifert R, Schwärzel M, Möglich A (2016) A fluorometric activity assay for light-regulated cyclic-nucleotide-monophosphate actuators. Methods Mol Biol 1408: 93-105. https://doi.org/:10.1007/978-1-4939-3512-3_7

Wojtovich AP, Foster TH (2014) Optogenetic control of ROS production. Redox Biol 2: 368-376. https://doi.org/:10.1016/j.redox.2014.01.019

Bilan DS, Pase L, Joosen L, Gorokhovatsky AY, Ermakova YG, Gadella T, Grabher C, Schultz C, Lukyanov S, Belousov VV (2013) HyPer-3: a genetically encoded H2O2 probe with improved performance for ratiometric and fluorescence lifetime imaging. ACS Chem Biol 8(3): 535-542. https://doi.org/:10.1021/cb300625g

Covington HE, Lobo MK, Maze I, Vialou V, Hyman JM, Zaman S, LaPlant Q, Mouzon E, Ghose S, Tamminga CA., Neve RL, Deisseroth K, Nestler EJ (2010) Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex. J Neurosci 30(48): 16082-16090. https://doi.org/:10.1523/JNEUROSCI.1731-10.2010

Haubensak W, Kunwar PS., Cai H, Ciocchi S, Wall NR, Ponnusamy R, Biag J, Dong H, Deisseroth K, Callaway EM, Fanselow MS, Lüthi A, Anderson DJ (2010) Genetic dissection of an amygdala microcircuit that gates conditioned fear. Nature 468(7321): 270-276. https://doi.org/:10.1038/nature09553

Velema A, Szymanski W, Feringa BL (2014) Photopharmacology: beyond proof of principle. J American Chem Soc 136(6): 2178-2191. https://doi.org/:10.1021/ja413063e

Mitscherlich E (1834) Uber das stickstoffbenzid. Ann der Physik 108(15): 225-227.

Hartley GS (1937) The cis-form of azobenzene. Nature 140(3537): 281-281.

Merino E, Ribagorda M (2012) Control over molecular motion using the cis–trans photoisomerization of the azo group. Beilstein J Org Chem 8(1): 1071-1090. https://doi.org/:10.3762/bjoc.8.119

Koshima H, Ojima N, Uchimoto H (2009) Mechanical motion of azobenzene crystals upon photoirradiation. J Am Chem Soc 131(20): 6890-6891. https://doi.org/:10.1021/ja8098596

Irie M (2000) Diarylethenes for memories and switches. Chem Rev 100(5): 1685-1716. https://doi.org/:10.1021/cr980069d

Lubbe AS, Szymanski W, Feringa BL (2017) Recent developments in reversible photoregulation of oligonucleotide structure and function. Chem Soc Rev 46(4): 1052-1079. https://doi.org/:10.1039/c6cs00461j

Klajn R (2014) Spiropyran-based dynamic materials. Chem Soc Rev. 43(1): 148-184. https://doi.org/:10.1039/c3cs60181a.

Lin WC, Kramer RH (2018) Light-Switchable Ion Channels and Receptors for Optogenetic Interrogation of Neuronal Signaling. Bioconjug Chem 29(4): 861-869. https://doi.org/:10.1021/acs.bioconjchem.7b00803

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. https://doi.org/:10.1152/jn.00251.2011

Leippe P, Winter N, Sumser MP, Trauner D (2018) Optical control of a delayed rectifier and a two-pore potassium channel with a photoswitchable bupivacaine. ACS Chem Neurosci 9(12): 2886-2891. https://doi.org/:10.1021/acschemneuro.8b00279

Trads JB., Hüll K, Matsuura BS., Laprell L, Fehrentz T, Görldt N, Kozek KA, Weaver CD., Klöcker N, Barber DM, Trauner D (2019) Sign inversion in photopharmacology: Incorporation of cyclic azobenzenes in photoswitchable potassium channel blockers and openers. Angew Chem Int Ed Engl 58(43): 15421-15428. https://doi.org/:10.1002/anie.201905790

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. https://doi.org/:10.1038/nchembio756

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 104(26): 10865–10870. https://doi.org/:10.1073/pnas.0701274104

Laprell L, Repak E, Franckevicius V, Hartrampf F, Terhag J, Hollmann M, Sumser M, Rebola N, DiGregorio DA, Trauner D (2015) Optical control of NMDA receptors with a diffusible photoswitch. Nat Commun. 6(1): 1-11. https://doi.org/:10.1038/ncomms9076

Donthamsetti PC, Winter N, Schönberger M, Levitz J, Stanley C, Javitch JA, Isacoff EY, Trauner D (2017) Optical control of dopamine receptors using a photoswitchable tethered inverse agonist. J Am Chem Soc 139(51): 18522-18535. https://doi.org/:10.1021/jacs.7b07659

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 U S A 110(51): 20813-20818. https://doi.org/:10.1073/pnas.1318715110

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. https://doi.org/:10.1038/nchem.1234

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(42): 10500-10504. https://doi.org/:10.1002/anie.201205475

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(1): 1-12. https://doi.org/:10.1038/ncomms2094

Maleeva G, Wutz D, Rustler K, Nin‐Hill A, Rovira C, Petukhova E, Bautista-Barrufet A, Gomila-Juaneda A, Scholze P, Peiretti F, Alfonso‐Prieto M, König B, Gorostiza P, Bregestovski P (2019) A photoswitchable GABA receptor channel blocker. Br J Pharmacol 176(15): 2661-267. https://doi.org/:10.1111/bph.14689

Rustler K, Maleeva G, Gomila AM, Gorostiza P, Bregestovski P, König B (2020) Optical Control of GABAA Receptors with a Fulgimide‐Based Potentiator. Chemistry 26(56): 12722-12727. https://doi.org/:10.1002/chem.202000710

Maleeva G, Nin-Hill A, Rustler K, Petukhova E, Ponomareva D, Mukhametova E, Gomila-Juaneda A, Wutz D, Alfonso-Prieto M, König B, Gorostiza P, Bregestovski P (2021) Subunit-specific photocontrol of glycine receptors by azobenzene-nitrazepam photoswitcher. eNeuro 8(1). https://doi.org/:10.1523/ENEURO.0294-20.2020

Gomila AM, Rustler K, Maleeva G, Nin-Hill A, Wutz D, Bautista-Barrufet A, Rovira X, Bosch M, Mukhametova E, Petukhiva E, Ponomareva D, Mukhamedyarov M, Peiretti F, Alfonso-Prieto M, Rovira C, König B, Bregestovski P, Gorostiza P (2020) Photocontrol of endogenous glycine receptors in vivo. Cell Chem Biol 27(11): 1425-1433. https://doi.org/:10.1016/j.chembiol.2020.08.005

Thompson AJ., Lester HA, Lummis SC (2010) The structural basis of function in Cys-loop receptors. Q Rev Biophys 43(4): 449-499. https://doi.org/:10.1017/S0033583510000168

Ortells MO. Lunt GG (1995) Evolutionary history of the ligand-gated ion-channel superfamily of receptors. Trends Neurosci 18(3): 121-127. https://doi.org/:10.1016/0166-2236(95)93887-4

Karlin A, Akabas MH (1995) Toward a structural basis for the function of nicotinic acetylcholine receptors and their cousins. Neuron 15(6): 1231-1244.

Вульфиус ЕА (2006) α7-Подтип нейрональных никотиновых рецепторов ацетилхолина: структура, свойства, распространение, функции. Биол мембр 23(2): 111-118 [Vulfius CA (2006) α7-subtype of neuronal nicotinic acetylcholine receptors: structure, properties, distribution, functions. Biol Membr 23(2): 111-118 (In Russ)].

Малеева ГВ, Брежестовский ПД (2014) Молекулярная физиология рецепторов глицина в нервной системе позвоночных. Рос физиол журн им И.М. Сеченова 100(3): 274-300 [Maleeva GV, Bregestovski PD (2014) Molecular physiology of glycine receptors in nervous system of vertebrates. Russ J Physiol 100(3): 274-300 (In Russ)].

Millar NS., Gotti C (2009) Diversity of vertebrate nicotinic acetylcholine receptors. Neuropharmacology 56(1): 237-246. https://doi.org/:10.1016/j.neuropharm.2008.07.041

Karlin A (2002) Emerging structure of the nicotinic acetylcholine receptors. Nat Rev Neurosci 3(2): 102-114. https://doi.org/:10.1038/nrn731

Changeux JP (2012) The nicotinic acetylcholine receptor: the founding father of the pentameric ligand-gated ion channel superfamily. J Biol Chem 287(48): 40207-40215. https://doi.org/:10.1074/jbc.R112.407668

Miledi R (1960) Junctional and extrajunctional acetylcholine receptors in skeletal muscle fibres. J Physiol 151(1): 24-30.

Mishina M, Takai T, Imoto K, Noda M, Takahashi T, Numa S, Methfessel C, Sakmann B (1986) Molecular distinction between fetal and adult forms of muscle acetylcholine receptor. Nature 321(6068): 406-411.

Hall ZW, Sanes JR (1993) Synaptic structure and development: the neuromuscular junction. Cell 72: 99-121.

McGehee DS, Role LW (1995) Physiological diversity of nicotinic acetylcholine receptors expressed by vertebrate neurons. Annu Rev Physiol 57(1): 521-546.

Kalamida D, Poulas K, Avramopoulou V, Fostieri E, Lagoumintzis G, Lazaridis K, Sideri A, Zouridakis M, Tzartos SJ (2007) Muscle and neuronal nicotinic acetylcholine receptors. Structure, function and pathogenicity. FEBS J 274(15): 3799-3845. https://doi.org/:10.1111/j.1742-4658.2007.05935.x

Gotti C, Zoli M, Clementi F (2006) Brain nicotinic acetylcholine receptors: native subtypes and their relevance. Trends Pharmacol Sci 27(9): 482-491. https://doi.org/:10.1016/j.tips.2006.07.004

Hogg RC, Raggenbass M, Bertrand D (2003) Nicotinic acetylcholine receptors: from structure to brain function. Rev Physiol Biochem Pharmacol 147: 1-46. https://doi.org/:10.1007/s10254-003-0005-1

Benowitz NL (2009) Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics. Annu Rev Pharmacol Toxicol 49: 57-71. https://doi.org/:10.1146/annurev.pharmtox.48.113006.094742

Dani JA, De Biasi M (2013) Mesolimbic dopamine and habenulo-interpeduncular pathways in nicotine withdrawal. Cold Spring Harb Perspect Med 3(6): a012138. https://doi.org/:10.1101/cshperspect.a012138

Posadas I, López-Hernández B, Ceña V (2013) Nicotinic receptors in neurodegeneration. Curr Neuropharmacol 11(3): 298-314. https://doi.org/:10.2174/1570159X11311030005

Deal WJ, Erlanger BF, Nachmansohn D (1969) Photoregulation of biological activity by photochromic reagents, III. Photoregulation of bioelectricity by acetylcholine receptor inhibitors. Proc Natl Acad Sci U S A. 64(4): 1230-1234. https://doi.org/:10.1073/pnas.64.4.1230

Conti-Tronconi BM, Hunkapiller MW, Lindstrom JM., Raftery MA (1982) Subunit structure of the acetylcholine receptor from Electrophorus electricus. Proc Natl Acad Sci U S A 79(21): 6489-6493.

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

Damijonaitis A, Broichhagen J, Urushima T, Hüll K, Nagpal J, Laprell L, Schönberger M, Woodmansee DH, Rafiq A, Sumser MP., Kummer W, Gottschalk A, Kummer W (2015) AzoCholine enables optical control of alpha 7 nicotinic acetylcholine receptors in neural networks. ACS Chem Neurosci 6(5): 701-707. https://doi.org/:10.1021/acschemneuro.5b00030

Karlin A (1969) Chemical modification of the active site of the acetylcholine receptor. J Gen Physiol 54(1): 245-264.

Bregestovski PD., Iljin VI, Jurchenko OP, Veprintsev BN, Vulfius CA (1977) Acetylcholine receptor conformational transition on excitation masks disulphide bonds against reduction. Nature 270(5632): 71-73.

Sheridan RE, Lester HA (1982) Functional stoichiometry at the nicotinic receptor. The photon cross section for phase 1 corresponds to two bis-Q molecules per channel. J Gen Physiol 80(4): 499-515.

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

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.

Krouse ME, Lester HA, Wassermann NH, Erlanger BF (1985) Rates and equilibria for a photoisomerizable antagonist at the acetylcholine receptor of Electrophorus electroplaques. J Gen Physiol 86(2): 235-256.

Chabala LD, Gurney AM, Lester HA (1986) Dose-response of acetylcholine receptor channels opened by a flash-activated agonist in voltage-clamped rat myoballs. J Physiol 371(1): 407-433.

Celie PH, van Rossum-Fikkert SE, van Dijk WJ, Brejc K, Smit AB, Sixma TK (2004) Nicotine and carbamylcholine binding to nicotinic acetylcholine receptors as studied in AChBP crystal structures. Neuron 41(6): 907-914. https://doi.org/:10.1016/s0896-6273(04)00115-1

Sieghart W (1995) Structure and pharmacology of g‐aminobutyric acid A receptor subtypes. Pharmacol Rev 47: 181-234.

Knoflach F, Hernandez MC, Bertrand D (2016) GABAA receptor-mediated neurotransmission: Not so simple after all. Biochem Pharmacol 115: 10-17. https://doi.org/:10.1016/j.bcp.2016.03.014

Sieghart W, Sperk G (2002) Subunit composition, distribution and function of GABAA receptor subtypes. Curr Top Med Chem 2(8): 795-816. https://doi.org/:10.2174/1568026023393507

Somogyi P, Tamas G, Lujan R, Buhl EH (1998) Salient features of synaptic organisation in the cerebral cortex. Brain Res Brain Res Rev 26(2-3): 113-135.

Salzman C (1998) Addiction to benzodiazepines. Psy Quart 69: 251–261.

Calcaterra NE, Barrow JC (2014) Classics in chemical neuroscience: diazepam (valium). ACS Chem Neurosci 5(4): 253-260. https://doi.org/:10.1021/cn5000056

Chang-Sheng SC, Olcese R, Olsen RW (2003) A single M1 residue in the β2 subunit alters channel gating of GABAA receptor in anesthetic modulation and direct activation. J Biol Chem 278(44): 42821-42828. https://doi.org/:10.1074/jbc.M306978200

Bali M, Akabas MH (2004) Defining the propofol binding site location on the GABAA receptor. Mol Pharmacol 65(1): 68-76. https://doi.org/:10.1124/mol.65.1.68

Wisden W, Korpi ER, Bahn S (1996) The cerebellum: a model system for studying GABAA receptor diversity. Neuropharmacology 35(9-10): 1139-1160.

Mäkelä J, Iivanainen M, Pieninkeroinen IP, Waltimo O, Lahdensuu M (1993) Seizures associated with propofol anesthesia. Epilepsia 34(5), 832-835.

Yamakura T, Sakimura K, Shimoji K, Mishina M (1995) Effects of propofol on various AMPA-, kainate-and NMDA-selective glutamate receptor channels expressed in Xenopus oocytes. Neurosci Lett 188(3): 187-190.

Vasileiou I, Xanthos T, Koudouna E, Perrea D, Klonaris C, Katsargyris A, Papadimitriou L (2009) Propofol: a review of its non-anaesthetic effects. Eur J Pharmacol 605(1-3): 1-8. https://doi.org/:10.1016/j.ejphar.2009.01.007

Wu Q, Zhao Y, Chen X, Zhu M, Miao C (2018) Propofol attenuates BV2 microglia inflammation via NMDA receptor inhibition. Can J Physiol Pharmacol 96(3): 241-248. https://doi.org/:10.1139/cjpp-2017-0243

Walder B, Tramèr MR, Seeck M (2002) Seizure-like phenomena and propofol: a systematic review. Neurology 58(9): 1327-1332. https://doi.org/:10.1212/wnl.58.9.1327

Lin W C, Davenport CM, Mourot A, Vytla D, Smith CM, Medeiros KA, Chambers JJ, Kramer RH (2014) Engineering a light-regulated GABAA receptor for optical control of neural inhibition. ACS Chem Biol 9(7): 1414-1419. https://doi.org/:10.1021/cb500167u

Lin WC, Tsai MC, Davenport CM, Smith CM, Veit J, Wilson NM, Adesnik H, Kramer RH (2015) A comprehensive optogenetic pharmacology toolkit for in vivo control of GABAA receptors and synaptic inhibition. Neuron 88(5): 879-891. https://doi.org/:10.1016/j.neuron.2015.10.026

Huckvale R, Mortensen M, Pryde D, Smart TG, Baker JR (2016) Azogabazine; a photochromic antagonist of the GABA A receptor. Org Biomol Chem 14(28): 6676-6678. https://doi.org/:10.1039/c6ob01101b

Chambon JP, Feltz P, Heaulme M, Restle S, Schlichter R, Biziere K, Wermuth CG (1985) An arylaminopyridazine derivative of gamma-aminobutyric acid (GABA) is a selective and competitive antagonist at the GABAA receptor site. Proc Natl Acad Sci U S A 82(6): 1832-1836.

Lin WC, Tsai MC, Rajappa R, Kramer RH (2018) Design of a highly bistable photoswitchable tethered ligand for rapid and sustained manipulation of neurotransmission. J Am Chem Soc 140(24): 7445-7448. https://doi.org/:10.1021/jacs.8b03942

Gastaut H, Naquet R, Poire R, Tassinari CA (1965) Treatment of status epilepticus with diazepam (Valium). Epilepsia 6(2): 167-182.

Tan KR, Rudolph U, Lüscher C (2011) Hooked on benzodiazepines: GABAA receptor subtypes and addiction. Trends Neurosci. 34(4): 188-197. https://doi.org/:10.1016/j.tins.2011.01.004

Rogawski MA, Heller AH (2019) Diazepam buccal film for the treatment of acute seizures. Epilepsy Behav 101(Pt B): 106537. https://doi.org/:10.1016/j.yebeh.2019.106537

Vitanova L, Haverkamp S, Wässle H (2014) Immunocytochemical localization of glycine and glycine receptors in the retina of the frog Rana ridibunda. Cell Tissue Res 317(3): 227-235. https://doi.org/:10.1007/s00441-004-0914-6

Danglot L, Rostaing P, Triller A, Bessis A (2004) Morphologically identified glycinergic synapses in the hippocampus. Mol Cell Neurosci 27(4): 394-403. https://doi.org/:10.1016/j.mcn.2004.05.007

Brackmann M, Zhao C, Schmieden V, Braunewell KH (2004) Cellular and subcellular localization of the inhibitory glycine receptor in hippocampal neurons. Biochem Biophys Res Commun 324(3): 1137-1142. https://doi.org/:10.1016/j.bbrc.2004.09.172

Xu T-L, Gong N (2010) Glycine and glycine receptor signaling in hippocampal neurons: diversity, function and regulation. Prog Neurobiol 91(4): 349-361. https://doi.org/:10.1016/j.pneurobio.2010.04.008

Chattipakorn SC, McMahon LL (2003) Strychnine-sensitive glycine receptors depress hyperexcitability in rat dentate gyrus. J Neurophysiol 89(3): 1339-1342. https://doi.org/:10.1152/jn.00908.2002

Leite JF, Cascio M (2001) Structure of ligand-gated ion channels: critical assessment of biochemical data supports novel topology. Mol Cell Neurosci 17(5): 777-792. https://doi.org/:10.1006/mcne.2001.0984

Friauf E, Hammerschmidt B, Kirsch J (1997) Development of adult-type inhibitory glycine receptors in the central auditory system of rats. J Comp Neurol 385(1): 117-134.

Malosio M, Marqueze B, Pouey A, Kuhse J, Betz H (1991) Widespread expression of glycine receptor subunit mRNAs in the adult and developing rat brain. EMBO J 10(9): 2401-2409.

Baer K, Waldvogel HJ, Faull RLM, Rees MI (2009) Localization of glycine receptors in the human forebrain, brainstem, and cervical spinal cord: an immunohistochemical review. Front Mol Neurosci 4(2): 25. https://doi.org/:10.3389/neuro.02.025.2009

Grenningloh G, Rienitz A, Schmitt B, Methfessel C, Zensen M, Beyreuther K, Gundelfinger ED, Betz H (1988) Molecular cloning of the antagonist-binding subunit of the glycine receptor. J Recept Res 8(1-4): 183-193.

Becker CM, Hoch W, Betz H (1988) Glycine receptor heterogeneity in rat spinal cord during postnatal development. EMBO J 7(12): 3717-3726.

Grenningloh G, Schmieden V, Schofield PR, Seeburg PH, Siddique T, Mohandas TK, Becker CM, Betz H (1990) Alpha subunit variants of the human glycine receptor: primary structures, functional expression and chromosomal localization of the corresponding genes. EMBO J 9(3): 771-776.

David-Watine B, Goblet C, De Saint Jan D, Fucile S, Devignot V, Bregestovski P, Korn H (1999) Cloning, expression and electrophysiological characterization of glycine receptor alpha subunit from zebrafish. Neuroscience 90(1): 303-317.

Imboden M, De Saint Jan D, Leulier F, Korn H, Goblet C, Bregestovski P (2001) Isolation and characterization of an alpha 2-type zebrafish glycine receptor subunit. Neuroscience 103(3): 799-810. https://doi.org/:10.1016/s0306-4522(00)00575-3

Devignot V, Prado de Carvalho L, Bregestovski P, Goblet C (2003) A novel glycine receptor αZ1 subunit variant in the zebrafish brain. Neuroscience 122(2): 449-457. https://doi.org/:10.1016/s0306-4522(03)00171-4

Grenningloh G, Pribilla I, Prior P, Multhaup G, Beyreuther K, Taleb O, Betz H (1990) Cloning and expression of the 58 kd beta subunit of the inhibitory glycine receptor. Neuron 4(6): 963-970.

Bormann J, Rundström N, Betz H, Langosch D (1994) Residues within transmembrane segment M2 determine chloride conductance of glycine receptor homo- and hetero-oligomers. EMBO J 12(10): 3729-3737.

Meyer G, Kirsch J, Betz H, Langosch D (1995) Identification of a Gephyrin Binding Motif on the Glycine Receptor p Subunit. Neuron 15(3): 563-572.

Kirsch J, Betz H (1995) The Postsynaptic Protein Gephyrin Localization Is Regulated of the Glycine Receptor-Associated by the Cytoskeleton. J Neurosci 715(6): 4148-4156.

Kneussel M, Betz H (2000) Clustering of inhibitory neurotransmitter receptors at developing postsynaptic sites: the membrane activation model. Trends Neurosci 23(9): 429-435. https://doi.org/:10.1016/s0166-2236(00)01627-1

Pribilla I, Takagi T, Langosch D, Bormann J, Betz H, Pribilla I (1992) The atypical M2 segment of the subunit confers picrotoxinin resistance to inhibitory glycine receptor channels. EMBO J 11(12): 4305-4311.

Zhorov BS, Bregestovski PD (2000) Chloride channels of glycine and GABA receptors with blockers: Monte Carlo minimization and structure-activity relationships. Biophys J 78(4): 1786-1803. https://doi.org/:10.1016/S0006-3495(00)76729-4

Kirsch J, Meyer G, Betz H (1996) Synaptic Targeting of Ionotropic Neurotransmitter Receptors. Mol Cell Neurosci 8(2-3): 93-98.

Singer JH, Berger AJ ( 2000) Development of inhibitory synaptic transmission to motoneurons. Brain Res Bull 53(5): 553-560. https://doi.org/:10.1016/s0361-9230(00)00389-0

Singer JH, Talley EM, Bayliss DA, Berger AJ (1998) Development of glycinergic synaptic transmission to rat brain stem motoneurons. J Neurophysiol 80(5): 2608-2620.

Mukhtarov M, Ragozzino D, Bregestovski P (2005) Dual Ca2+ modulation of glycinergic synaptic currents in rodent hypoglossal motoneurones. J Physiol 569(3): 817-831. https://doi.org/:10.1113/jphysiol.2005.094862

Akagi H, Miledi R (1988) Heterogeneity of glycine receptors and their messenger RNAs in rat brain and spinal cord. Science 242(4876): 270-273.

Becker CM, Hoch W, Betz H (1988) Glycine receptor heterogeneity in rat spinal cord during postnatal development. EMBO J 7(12): 3717-3726.

Samanta S, Beharry AA, Sadovski O, McCormick TM, Babalhavaeji A, Tropepe V, Woolley GA (2013) Photoswitching azo compounds in vivo with red light. J Am Chem Soc 135(26): 9777-9784. https://doi.org/:10.1021/ja402220t