Kazan medical journalKazan medical journalКазанский медицинский журнал0368-48142587-9359Eco-Vector1101910.17816/KMJ2018-158ReviewsОбзорыReview ArticleOptogenetics and photopharmacology - effective tools for managing cell activity using lightОптогенетика и фотофармакология - эффективные инструменты управления активностью клеток с помощью светаBregestovskiP DБрежестовскийПётр Дмитриевичpbreges@gmail.comZefirovA LЗефировАндрей Львовичpbreges@gmail.comInstitute of Neurosciences, Kazan State Medical UniversityИнститут нейронаук, Казанский государственный медицинский университетInstitut de Neurosciences des Systèmes, Aix-Marseille UniversityИнститут системных нейронаук, Университет Экс-Марсель080220191001VOL 100, NO1 (2019)ТОМ 100, №1 (2019)15816908022019Copyright ©; 2019, Bregestovski P.D., Zefirov A.L.Copyright ©; 2019, Брежестовский П.Д., Зефиров А.Л.2019Bregestovski P.D., Zefirov A.L.Брежестовский П.Д., Зефиров А.Л.http://creativecommons.org/licenses/by-nc-sa/4.0https://kazanmedjournal.ru/kazanmedj/article/view/11019

Contemporary research has been enriched by the new directions in which the light plays a key role as a tool for modulation of cellular activity and invasive monitoring of intracellular ions and other components. The main advantages of these approaches are the possibilities to precisely control the intensity, spectral characteristics and durations of light signals in space and time. This review summarizes the key areas, optogenetics and photopharmacology, - directions that allow to control cellular activity with light. Optogenetics is the use of light-sensitive transmembrane proteins capable of exciting or inhibiting cellular activity under illumination by different wavelengths. In 2003 a light-sensitive protein canalo-rodopsine was isolated and cloned which is capable of inducing ion currents and changing cellular rest potential with its excitation under the blue light when embedded into the neurons or other cell types. Inhibition of cellular activity is caused by expression of other lightsensitive proteins - chloride or hydrogen pumps, or anion-selective ion channels. These principles turns out to be efficacious for the study of the functions of solitary cells and neural nets as well as for the control of living organisms behavior but their use in medicine is complicated because of necessary genetic manipulations. Photopharmacology is based on creating and using of chemical compounds changing conformations and/or activity under the light. Photochromic compounds with the use of photosensitive switches are capable of selective activation or inhibition of the activity of functionally important proteins - receptors, ion channels, enzymes, etc. The principles and the potential use of optogenetics and photopharmacology in the analysis of the neuronal functions and the perspectives for new approaches to treat some diseases of the nervous system are discussed.

Современные исследования обогатились перспективными научно-технологическими направлениями, в которых свет играет ключевую роль как инструмент модуляции клеточной активности и инвазивного мониторинга внутриклеточных ионов и других компонентов. Основное преимущество этих подходов - возможность точного управления интенсивностью, спектральными характеристиками и длительностью световых сигналов в пространстве и времени. В обзоре кратко представлены основные направления - оптогенетика и фотофармакология, обеспечивающие управление активностью клеток с помощью света. Оптогенетика - использование светочувствительных трансмембранных белков, способных вызывать возбуждение или ингибирование клеточной активности при освещении различными длинами волн. В 2003 г. был выделен и клонирован светочувствительный белок каналородопсин, который при встраивании в нейроны или другие типы клеток способен под действием голубого света индуцировать ионные токи и изменять потенциал покоя клеток, вызывая их возбуждение. Торможение клеточной активности обеспечивается встраиванием других светочувствительных белков - хлорных или водородных насосов, или анион-избирательных ионных каналов. Эти принципы оказались плодотворными для изучения функций одиночных клеток и нейрональных сетей, а также контроля поведения живых организмов, однако их использование в медицине пока затруднено из-за необходимости генетических манипуляций. Фотофармакология основана на создании и использовании химических соединений, изменяющих конформации и/или активность под действием света. Фотохромные соединения с помощью светочувствительных переключателей способны избирательно активировать или угнетать активность функционально важных белковых молекул - рецепторов, ионных каналов, ферментов и др. В работе освещены принципы и потенциальные возможности использования оптогенетики и фотофармакологии в анализе функций нервных клеток и перспективы в поиске новых путей лечения некоторых заболеваний нервной системы.

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