vestnik-bio-msuВестник Московского университета. Серия 16. БиологияVestnik Moskovskogo universiteta. Seriya 16. Biologiya0137-0952Lomonosov Moscow State University, School of Biology10.55959/MSU0137-0952-16-79-2S-4vestnik-bio-msu-1378Research ArticleОБЗОРREVIEWСовременные представления о структурной основе и молекулярных механизмах трансмембранного транспорта Сl- в кардиомиоцитахStructural basis and molecular mechanisms of Cl- transmembrane transport in cardiomyocyteshttps://orcid.org/0000-0001-6624-7805ВоронинаЯ. А.VoroninaY. A.

Воронина Яна Алексеевна – ассистент кафедры физиологии человека и животных биологического факультета, 119234, г. Москва, ул. Ленинские горы, д. 1, стр. 12;

121552, г. Москва, ул. Академика Чазова, д. 15а

Faculty of Biology, Leninskie gory 1–12, Moscow, 119234;

st. Academician Chazova, 15a, Moscow, 121552

voronina.yana.2014@post.bio.msu.ruhttps://orcid.org/0000-0003-0919-0712КарховА. М.KarhovA. M.

Кархов Андрей Михайлович – студент магистратуры кафедры физиологии человека и животных биологического факультета, 119234, г. Москва, ул. Ленинские горы, д. 1, стр. 12;

121552, г. Москва, ул. Академика Чазова, д. 15а

Faculty of Biology, Leninskie gory 1–12, Moscow, 119234;

st. Academician Chazova, 15a, Moscow, 121552

akarchoff@gmail.comhttps://orcid.org/0000-0003-3075-4834КузьминВ. С.KuzminV. S.

Кузьмин Владислав Стефанович – докт. биол. наук, проф. кафедры физиологии человека и животных биологического факультета, 119234, г. Москва, ул. Ленинские горы, д. 1, стр. 12;

121552, г. Москва, ул. Академика Чазова, д. 15а

Faculty of Biology, Leninskie gory 1–12, Moscow, 119234;

st. Academician Chazova, 15a, Moscow, 121552

ku290381@mail.ruМосковский государственный университет имени М.В. Ломоносова; Научно-исследовательский институт экспериментальной кардиологии имени академика В.Н. Смирнова, Национальный медицинский исследовательский центр кардиологии имени академика Е.И. Чазова Минздрава РоссииРоссияLomonosov Moscow State University; Academician Smirnov Institute of Experimental Cardiology, Academician Chazov National Medical Research Centre of CardiologyRussian Federation202423082024792S2236Copyright © Воронина Я.А., Кархов А.М., Кузьмин В.С., 20242024Воронина Я.А., Кархов А.М., Кузьмин В.С.Voronina Y.A., Karhov A.M., Kuzmin V.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestnik-bio-msu.elpub.ru/jour/article/view/1378

Внутриклеточная концентрация анионов хлора ([Cl-]i), равновесный потенциал для анионов хлора (ECl), а также трансмембранные хлорные токи (ICl) являются факторами, которые оказывают значительное влияние на электрофизиологические свойства возбудимой ткани, в том числе, миокарда. К настоящему моменту в сердце выявлено несколько типов хлорной (анионной) проводимости. В последние годы идентифицирован целый ряд трансмембранных белков, демонстрирующих хлорную проводимость (CFTR, ClC, TMEM16, LRRC8), а также подтверждена экспрессия этих макромолекул в ткани сердца. Накопленные данные позволяют установить молекулярный субстрат для некоторых хлорных анионных токов (ICl,PKA, ICl,ir, ICl,vol, ICl,swell, ICl,Ca, Ito2), обнаруживаемых в сердце. Кроме того, установлены молекулярные механизмы регуляции [Cl-]i и ECl посредством хлорных котранспортеров (КСС, NKCC1) и хлор-бикарбонатных обменников. Множественность структур, определяющих хлорную трансмембранную проводимость, и сложность молекулярных механизмов регуляции хлорного гомеостаза лежат в основе комплексных и зачастую разнонаправленных эффектов активации хлорных переносчиков в ритмоводителе, проводящей системе и рабочем миокарде сердца. В данном обзоре рассмотрены структурные и биофизические свойства, а также молекулярная регуляция белковых комплексов – переносчиков хлора, идентифицированных в миокарде.

The intracellular concentration of chlorine anions ([Cl-]i), the equilibrium potential for chlorine anions (ECl) and transmembrane chloride currents (ICl) are the factors that significantly influence the electrophysiological properties of excitable tissue, including the myocardium. Several types of chloride (anion) conductance have been identified in the heart. In recent years, a number of transmembrane proteins demonstrating chloride conductance have been identified (CFTR, ClC, TMEM16, LRRC8), and the expression of these macromolecules in cardiac tissue has been confirmed. Accumulated data allow for establishing a molecular substrate for some chloride anion currents (ICl,PKA, ICl,ir, ICl,vol, ICl,swell, ICl,Ca, Ito2) detected in the heart. Furthermore, the molecular mechanisms regulating [Cl-]i and ECl through chloride cotransporters (KCC, NKCC1) and chloride-bicarbonate exchangers have been established. The variety of structures determining chloride transmembrane conductivity and the complexity of molecular mechanisms regulating chloride homeostasis underlie the complex effects of activation of chloride transporters in the pacemaker, conduction system and working myocardium of the heart. This review discusses the structural, biophysical properties and molecular regulation of chloride transporter protein complexes identified in the myocardium. The review also covers the mechanisms by which chloride transmembrane transport influences the bioelectrical activity of cardiomyocytes.

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The authors declare that there are no conflicts of interest present.