cardiovascularКардиоваскулярная терапия и профилактикаCardiovascular Therapy and Prevention1728-88002619-0125«SILICEA-POLIGRAF» LLCcardiovascular-1606Research ArticleОБЗОРЫREVIEWSПейсмекерные f-каналы миоцитов синусового узла, как новая терапевтическая мишень для снижения частоты сердечных сокращенийPace-maker f-channels of sinus node myocytеs as a new therapeutic target for heart rate reductionАсташкинЕ. И.AstashkinE. I.glezermg@mtu-net.ruГлезерМ. Г.GlezerM. G.glezermg@mtu-net.ruМосковская медицинская академия им. И.М.Сеченова, МоскваI.M. Sechenov Moscow Medical Academy, Moscow20070101197068106115Copyright © Асташкин Е.И., Глезер М.Г., 19701970Асташкин Е.И., Глезер М.Г.Astashkin E.I., Glezer M.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cardiovascular.elpub.ru/jour/article/view/1606

Контроль пейсмекерной активности сердца осуществляется высоко специализированными миоцитами синусового узла (СУ) и тесно связан с функциональной активностью f-каналов, через которые протекает If ток, переносимый катионами Na+ и К+ в цитоплазму клеток. Активация f каналов происходит при гиперполяризации плазматических мембран пейсмекерных клеток в области диастолических значений мембранного потенциала. Экспериментально продемонстрировано участие If тока в запуске процесса медленной диастолической деполяризации (ДД), а также в регуляции скорости протекания этого процесса под влиянием эндогенных нейромедиаторов и экзогенных химических агентов. Снижение количества открытых f-каналов уменьшает величину If тока, тормозит скорость ДД и увеличивает время достижения пороговых значений мембранного потенциала. Это обуславливает снижение частоты сердечных сокращений (ЧСС). Величина If тока контролируется также в результате прямого связывания с белками f-каналов циклического аденозинмонофосфата, уровень которого в цитоплазме миоцитов СУ изменяется под влиянием нейромедиаторов вегетативной нервной системы (ВНС); с помощью этого механизма ВНС регулирует ЧСС в физиологических условиях. Поиск химических агентов, избирательно влияющих на f-каналы, привел к созданию инновационного лекарственного препарата ивабрадина (Кораксан®), используемого для лечения стенокардии у пациентов с синусовым ритмом. Препарат снижает ЧСС за счет снижения If тока и увеличения продолжительности ДД. Уникальной особенностью ивабрадина служит отсутствие его влияния на другие виды ионных каналов.

Heart pace-maker activity is controlled by highly specialized sinus node (SN) myocytes. This control is linked to functional activity of f-channels providing Na+ and К+ If current. F-channels are activated by plasmatic membrane hyperpolarization in pace-maker cells, at diastolic values of membrane potential. Recent experiments have demonstrated that If current activates slow diastolic depolarization (DD) and regulates the rate of this process, together with endogenous neuromediators and exogenous chemical agents. Decrease in the quantity of open f-channels reduces If current, DD rate and increases threshold membrane potential time. As the result, heart rate (HR) decreases. If current is also controlled by cAMP binding to f-channel proteins. cAMP level in SN myocyte cytoplasma is influenced by autonomous nervous system (ANS) neuromediators. This is the mechanism for ANS regulation of HR in physiological settings. Search for chemical agents selectively targeting f-channels resulted in the development of a new medication, ivabradine (Coraxan®), which is used for angina treatment in patients with sinus rhythm. The medication decreases HR by If current reduction and DD time increase. Importantly, ivabradine does not affect other ion channels.

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