Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental NeurologyАнналы клинической и экспериментальной неврологии2075-54732409-2533Eco-Vector79810.54101/ACEN.2021.4.5Original articlesОригинальные статьиReview ArticleStructural pharmacology of GABAА receptorsСтруктурная фармакология ГАМКА-рецепторовhttps://orcid.org/0000-0001-7024-7461RossokhinAlexey V.РоссохинАлексей Владимирович
Russian Federation

Cand. Sci. (Phys.-Math.), leading researcher, Laboratory of functional synaptology

к.ф-м.н., в.н.с. лаб. функциональной синаптологии

alrossokhin@yahoo.comhttps://orcid.org/0000-0001-9955-1870SharonovaIrina N.ШароноваИрина Николаевна
Russian Federation

D. Sci. (Biol.), leading researcher, Laboratory of functional synaptology

д.б.н., в.н.с. лаб. функциональной синаптологии

alrossokhin@yahoo.comResearch Center of NeurologyФГБНУ «Научный центр неврологии»2312202115444532212202122122021Copyright ©; 2021, Rossokhin A.V., Sharonova I.N.Copyright ©; 2021, Россохин А.В., Шаронова И.Н.2021Rossokhin A.V., Sharonova I.N.Россохин А.В., Шаронова И.Н.https://creativecommons.org/licenses/by/4.0https://annaly-nevrologii.com/pathID/article/view/798

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian central nervous system (CNS), activating the inotropic type A receptors (GABAА receptors) to provide fast inhibition. GABAА receptors are the main target for various groups of drugs that are widely used in the treatment of CNS disorders.

This review examines the relationship between the physiological effects of GABAА receptor activation and modulation by various substances (including medicinal compounds), the receptor's structure, and the interaction of these substances with specific modulatory sites. Recent advances in cryogenic electron microscopy have led to fundamental improvements in understanding the detailed organization and function of GABAА receptors. This review is based on both the latest structural data obtained from cryogenic electron microscopy and the results of biochemistry and electrophysiology studies, as well as molecular modelling.

Гамма-аминомасляная кислота (ГАМК), основной тормозный нейромедиатор в центральной нервной системе (ЦНС) млекопитающих, активирует ионотропные рецепторы А типа (ГАМКАР), обеспечивающие процессы быстрого торможения. ГАМКАР являются основной мишенью для различных групп препаратов, широко используемых при лечении заболеваний ЦНС.

В обзоре представлены данные, позволяющие показать, как связаны физиологические эффекты, вызываемые активацией и модуляцией функций ГАМКАР различными веществами (в том числе относящимися к лекарственным соединениям), со структурой рецептора и с взаимодействием этих веществ с конкретными модуляторными сайтами. Недавний прогресс в криоэлектронной микроскопии привёл к фундаментальным достижениям в понимании детальной организации и механизмов функционирования ГАМКАР. Обзор основан как на современных структурных данных, полученных с помощью криоэлектронной микроскопии, так и на результатах исследований, выполненных при помощи биохимических и электрофизиологических методов, а также методов молекулярного моделирования.

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