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Photochromic Modulation of Cys-loop Ligand-gated Ion Channels

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Abstract

Advances in molecular and cellular biology, as well as the development of chemical synthesis and modern technologies, enriched the contemporary experimental research with new directions in which light plays a key role as a tool for modulating biological functions. One of them is photopharmacology, a field that uses chemically synthesized light-controlled compounds that can modulate the functions of proteins. When illuminated at specific wavelengths, these synthetic photoswitches are capable of modulating functions of receptors, ion channels and enzymes. This review briefly describes compounds that modulate the functions of ionotropic Cys-loop receptors for acetylcholine, GABA, and glycine. The nicotinic acetylcholine receptor (nAChR) is the first receptor-operated channel for which a way of modulation using light-dependent molecules has been discovered. In the 1970s–80s, blockers and activators of nAChR were created, consisting of azobenzene (light-controlled switch) and agonists. In the current millennium, new compounds have been created to provide light-controlled modulation of nAChR activity. These new photochromes are selective to muscle and neuronal nAChR, and are promising to study the physiological role of nAChRs in the nervous system. An extensive library of photochromic compounds is available for light-controlling of GABA receptor function. Some of them modulate the activity via interaction with the agonist site, the others are light-controlled blockers of chloride-selective ion channels. Recently, the first two photochromic modulators of glycine receptor activity have also been developed. These achievements demonstrate that photopharmacology opens up unique possibilities for remote control of physiological functions, as well as for studying the processes of inhibition and excitation in neural networks and models of neuronal pathologies.

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Abbreviations

nAChR:

nicotinic acetylcholine receptor

GABA:

gamma-aminobutyric acid

GABAR:

gamma-aminobutyric acid receptor

5-HT3P:

serotonin receptor

TM domain:

transmembrane domain

Azo-Ch:

azocholine

CNS:

central nervous system

HEK cells:

human embryonic kidney cells

UV:

ultraviolet

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This work was supported by the Russian Scientific Foundation (project no. 18-15-00313).

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  1. Institute of Neurosciences, Kazan State Medical University, Kazan, Russia

    P. D. Bregestovski & D. N. Ponomareva

  2. INSERM, INS, Institut de Neurosciences des Systèmes, Aix-Marseille University, Marseille, France

    P. D. Bregestovski & D. N. Ponomareva

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Russian Text © The Author(s), 2021, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2021, Vol. 107, Nos. 4–5, pp. 436–457https://doi.org/10.31857/S0869813921040051.

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Bregestovski, P.D., Ponomareva, D.N. Photochromic Modulation of Cys-loop Ligand-gated Ion Channels. J Evol Biochem Phys 57, 354–371 (2021). https://doi.org/10.1134/S0022093021020162

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