transmedТрансляционная медицинаTranslational Medicine2311-44952410-5155Almazov National Medical Research Centre, Saint Petersburg, Russia10.18705/2311-4495-2017-4-4-23-35transmed-304Research ArticleСЕРДЕЧНО-СОСУДИСТЫЕ ЗАБОЛЕВАНИЯCARDIOVASCULAR MEDICINEМОЛЕКУЛЯРНЫЕ МЕХАНИЗМЫ СИНДРОМА БРУГАДА ПОДТИПА 1MOLECULAR MECHANISMS OF BRUGADA SYNDOME SUBTYPE 1ЗайцеваА. К.ZaytsevaA. K.

м.н.с., Институт Молекулярной Биологии и Генетики, ул. Аккуратова, д. 2, Санкт-Петербург, 197341;

студент магистратуры, Санкт-Петербург

young research fellow,

Akkuratova str. 2, Saint Petersburg, 197341

zaytseva.anastasia.zak@gmail.comКарпушевА. В.KarpushevA. V.

к.б.н., с.н.с., Институт Молекулярной Биологии и Генетики,

 Санкт-Петербург

PhD, senior research fellow, 

Saint Petersburg

akarpushev@yandex.ruМихайловЕ. Н.MikhaylovE. N.

д.м.н., зав. НИЛ нейромодуляции,

 Санкт-Петербург

Evgeniy N. Mikhaylov, PhD, MD, head of the laboratory of neuromodulation, 

Saint Petersburg

mikhaylov_en@almazovcentre.ruЖоровБ. С.ZhorovB. S.

с.н.с.;

д.б.н., профессор, гл.н. сотр., 

 Санкт-Петербург

senior scientist;

Dr.Sc., prof., principal scientist,

Saint Petersburg

zhorov@mcmaster.caКостареваА. А.KostarevaA. A.

к.м.н., директор Института Молекулярной Биологии и Генетики,

 Санкт-Петербург

PhD, MD, head of the Institute of Molecular Biology and Genetics,

Saint Petersburg

akostareva@hotmail.comФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр им. В. А. Алмазова» Минздрава России; Санкт-Петербургский государственный университетРоссияAlmazov National Medical Research Centre; Saint Petersburg UniversityRussian FederationФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр им. В. А. Алмазова» Минздрава РоссииРоссияAlmazov National Medical Research CentreRussian FederationФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр им. В. А. Алмазова» Минздрава России; Федеральное государственное бюджетное учреждение науки «Институт эволюционной физиологии и биохимии им. И. М. Сеченова» Российской академии наукRussian FederationAlmazov National Medical Research Centre; Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of SciencesRussian Federation201707102017442335Copyright © Зайцева А.К., Карпушев А.В., Михайлов Е.Н., Жоров Б.С., Костарева А.А., 20172017Зайцева А.К., Карпушев А.В., Михайлов Е.Н., Жоров Б.С., Костарева А.А.Zaytseva A.K., Karpushev A.V., Mikhaylov E.N., Zhorov B.S., Kostareva A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://transmed.almazovcentre.ru/jour/article/view/304

Синдром Бругада – тяжелое наследственное аритмогенное заболевание. Несмотря на большое число данных, накопившихся с момента его открытия в 1992 году, до сих пор отсутствует понимание связи генотип-фенотип в проявлении и развитии данной патологии при миссенс-мутациях в гене SCN5A, кодирующем альфа-субъединицу потенциал-зависимых натриевых каналов Nav 1.5. Целью данного обзора является систематизация полученных за последние 25 лет данных по электрофизиологии, биофизическим и молекулярным механизмам возникновения дефектов функции канала Nav 1.5 при синдроме Бругада 1 типа. Рассмотрены клиническая картина, гипотезы развития данной аритмии на клеточном уровне и вклад изменений электрофизиологических параметров каналов Nav 1.5 в патологическое состояние. Описано влияние на активность мутантных форм канала фармакологических агентов и различных компонентов сигнальных путей в кардиомиоцитах. 

Brugada syndrome is a rare hereditary arrhythmogenic disorder first described by Brugada brothers in 1992. Despite the large amount of clinical and experimental data, there is no complete understanding of genotype-phenotype relation in pathogenesis of the disease caused by missence mutations in SCN5A, which encodes the alpha-subunit of the major cardiac voltage-gated sodium channel Nav 1.5. The aim of this review is to summarize current knowledge on molecular, cellular and ionic mechanisms of the Brugada syndrome development. We focused on the clinical picture and physiological consequences of decreasing activity of Nav 1.5 and analyzed the impact of biophysical properties alterations on the pathological state. The mutation-specific influence of pharmacological agents and signalling proteins was described. 

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