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Гайдуков Александр Евгеньевич

Факультет биологии и биотехнологии

Профиль на hse.ru ↗ тел.: 15474
Публикаций
13
Языков
2
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0
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0
Профиль Публикации (13) Курсы (2)

Профессиональные интересы

нейробиологияэлектрофизиология

Должности

  • Доцент — Факультет биологии и биотехнологии, Базовая кафедра Института биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова РАН

Био

  • · Начал работать в НИУ ВШЭ в 2020 году.

Образование

  • 2023 · Доктор биологических наук: Московский государственный университет им. М.В. Ломоносова
  • 2004 · Кандидат биологических наук: Московский государственный университет им. М.В. Ломоносова
  • 1997 · Специалитет: Московский государственный университет им. М.В. Ломоносова, специальность «Физиология», квалификация «Физиолог»

Опыт работы

  • · 2003 г. - по настоящее время: кафедра физиологии человека и животных биологического факультета МГУ имени М.В. Ломоносова (в настоящее время – в должности ведущего научного сотрудника)

Идентификаторы исследователя

Публикации (13)

Sortilin and L-type Calcium Channels May be Involved in the Unusual Mechanism of proBDNF Signaling in Regenerating Mouse Neuromuscular Junctions

2025 · ARTICLE · en

proBDNF and its main proteolytic product BDNF play crucial roles in maturation of neuromuscular junctions during development or reinnervation. We investigated the mechanisms of acute proBDNF effects on synaptic transmission in mouse motor synapses regenerating after nerve crush. The cleavage-resistant proBDNF mimicked the previously shown effect of cleavable proBDNF– GIRK-mediated decrease in the miniature endplate potential (MEPP) frequency accompanied by slight hyperpolarization of postsynaptic membrane. Remarkably, this effect did not utilize canonical proBDNF signaling pathway since inhibition of either p75 receptors with LM11A-31 or sortilin with AF38469 was not able to prevent it. Without sortilin activity, proBDNF downregulated the quantal content of multiquantal endplate potentials (EPP). This non-canonical action of proneurotrophin via TrkB receptors highlights the important role of sortilin as a safeguard preventing the spread of the negative effect of proBDNF on the evoked neurotransmitter release in regenerating motor synapses. In the absence of sortilin activity L-type calcium channels emerged as the key players providing proBDNF-induced decrease of EPP quantal content, while they were not involved in proBDNF-induced decrease of MEPP frequency. Sortilin-independent but TrkB- and GIRK-mediated inhibition of spontaneous release by proBDNF was not associated with the activity of acetylcholine (M2) or purinergic (A1 and P2Y13) metabotropic receptors. We propose that depending on sortilin involvement, proBDNF selectively affects spontaneous or evoked quantal neurotransmitter release via different branches of signaling pathway that ensure the presynaptic activation of GIRK or L-type calcium channels, respectively.

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Потенциал-зависимые кальциевые каналы в моторных синапсах млекопитающих – триггеры и модуляторы нервно-мышечной передачи

2024 · ARTICLE · ru

Запуск быстрой синхронной квантовой секреции нейротрансмиттеров в центральных и периферических синапсах обеспечивается за счет локального возрастания концентрации ионов Са2+ в нервных терминалях около Са2+-сенсоров синаптических везикул в ответ на деполяризацию пресинаптической мембраны распространяющимся по аксону потенциалом действия. Вход ионов Са2+ снаружи через пресинаптические потенциал-зависимые Са2+-каналы CaV2.1 или СaV2.2 (P/Q- или N-типа) – основной способ формирования динамического Са2+-сигнала, запускающего процесс экзоцитоза синаптических везикул практически во всех типах химических синапсов и способного индуцировать развитие определенных Са2+-зависимых форм синаптической пластичности. Однако в последние годы стало очевидным, что набор источников и спектр пресинаптических Са2+-сигналов весьма разнообразен. Выявление спектра регуляторных Са2+-входов, работающих в комплексе с соответствующими им мишенями, описание их вклада в механизмы, управляющие квантовой секрецией нейротрансмиттера, представляет собой актуальное направление современной синаптической физиологии. Cреди таких дополнительных к триггерному Са2+-входов особый интерес представляют Са2+-каналы L-типа, роль и условия активации которых в нервно-мышечных синапсах малоизучены и не дают однозначного представления о месте этого Са2+-входа в регуляции секреции ацетилхолина в моторных синапсах позвоночных. Данный обзор систематизирует имеющиеся на сегодняшний день результаты исследований многообразной функциональной роли потенциал-управляемых Са2+-каналов в нервно-мышечных синапсах млекопитающих и пресинаптических сигнальных путях, контролирующих эти Са2+-входы, и их участие в процессах тонкой настройки квантовой секреции ацетилхолина.

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ProBDNF and Brain-Derived Neurotrophic Factor Prodomain Differently Modulate Acetylcholine Release in Regenerating and Mature Mouse Motor Synapses

2022 · ARTICLE · en

The effects of brain-derived neurotrophic factor (BDNF) processing by-products (proBDNF and BDNF prodomain) on the activity of mouse neuromuscular junctions (NMJs) were studied in synapses formed during the reinnervation of extensor digitorum longus muscle (m. EDL) and mature synapses of the diaphragm. The parameters of spontaneous miniature endplate potentials (MEPPs) and evoked endplate potentials (EPPs) were analyzed in presence of each of the BDNF maturation products (both – 1 nM). In newly formed NMJs, proBDNF caused an increase in the resting membrane potential of muscle fibers and a decrease in the frequency of MEPPs, which was prevented by tertiapin-Q, a G-protein-coupled inwardly rectifying potassium channels (GIRK) blocker but not by p75 receptor signaling inhibitor TAT-Pep5. proBDNF had no effect on the parameters of EPPs. BDNF prodomain in newly formed synapses had effects different from those of proBDNF: it increased the amplitude of MEPPs, which was prevented by vesamicol, an inhibitor of vesicular acetylcholine (ACh) transporter; and reduced the quantal content of EPPs. In mature NMJs, proBDNF did not influence MEPPs parameters, but BDNF prodomain suppressed both spontaneous and evoked ACh release: decreased the frequency and amplitude of MEPPs, and the amplitude and quantal content of EPPs. This effect of the BDNF prodomain was prevented by blocking GIRK channels, by TAT-Pep5 or by Rho-associated protein kinase (ROCK) inhibitor Y-27632. At the same time, the BDNF prodomain did not show any inhibitory effects in diaphragm motor synapses of pannexin 1 knockout mice, which have impaired purinergic regulation of neuromuscular transmission. The data obtained suggest that there is a previously unknown mechanism for the acute suppression of spontaneous and evoked ACh release in mature motor synapses, which involves the activation of p75 receptors, ROCK and GIRK channels by BDNF prodomain and requires interaction with metabotropic purinoreceptors. In general, our results show that both the precursor of BDNF and the product of its maturation have predominantly inhibitory effects on spontaneous and evoked ACh release in newly formed or functionally mature neuromuscular junctions, which are mainly opposite to the effects of BDNF. The inhibitory influences of both proteins related to brain neurotrophin are mediated via GIRK channels of mouse NMJs.

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Spontaneous Acetylcholine Release Potentiation Induced by 2-Arachidonoylglycerol and Anandamide in Mouse Motor Synapses

2021 · ARTICLE · en

Changes in the parameters of miniature endplate potential (MEPP) of mouse diaphragm caused by exogenous application of two classical endocannabinoids, 2-arachidonoylglycerol (2-AG) (1 μM) and anandamide (AEA) (30 μM), were compared. A slowly developing stable increase in the MEPP amplitude by 50%, without affecting the frequency of MEPPs, was caused by 2-AG. This effect was prevented by AM-251, an inverse agonist of CB1-receptors, as well as by vesamicol, a blocker of the vesicular acetylcholine (ACh) transporter. On the contrary, AEA did not cause significant changes in the MEPP amplitude but induced a slowly developing (within 2 h) increase in MEPP frequency by 75% on average. The effect of AEA was prevented by AM-251 (1 μM) as well as by blocking of L-type Ca2+-channels with nitrendipine (1 μM) and inhibition of PKA activity by H89 (1 μM). It was concluded that both 2-AG and AEA are able to exert a noncanonical facilitating presynaptic effect on spontaneous ACh release. Even though these endocannabinoids activate the same type of CB-receptors, their facilitating effects do not overlap and are strictly aimed either at potentiating the size of ACh quanta (in case of 2-AG) or increasing the frequency of MEPP (in case of AEA). We assume that different intracellular targets and signaling pathways may be involved in the differentiated facilitating effects of 2-AG and AEA in mouse neuromuscular junctions.

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Биология. Основы анатомии и физиологии человека

2021 · BOOK · ru

Предлагаемое пособие — краткое, но емкое изложение основных сведений по анатомии и физиологии человека, которые являются важнейшей частью школьного курса биологии. Издание предназначено для учащихся старших классов, а также всех тех, кто решил сдать ЕГЭ по биологии либо другие формы вступительных испытаний, связанные с поступлением в медицинские, биологические, психологические и некоторые другие вузы. Пособие написано коллективом авторов — преподавателей МГУ имени М.В. Ломоносова, обладающих многолетним опытом преподавания соответствующих разделов биологии школьникам на самых разных уровнях: от обычных средних школ до сборных заключительного этапа Всероссийских олимпиад. Авторы последовательно характеризуют все системы организма человека: опорно-двигательную, иммунную, сердечно-сосудистую, дыхательную, пищеварительную, выделительную и т.д. Особое внимание уделяется сложным вопросам школьной биологии, связанным с регуляцией деятельности перечисленных систем за счет управляющих сигналов мозга и работы эндокринных желез. Темы строения и функций нервной системы, а также физиологических основ психических процессов раскрываются в заключительной части пособия. Большинство глав сопровождается оригинальными авторскими иллюстрациями.

The Participation of Endocannabinoid Receptors in the Regulation of Spontaneous Synaptic Activity at Neuromuscular Junctions of Mice

2020 · ARTICLE · en

The mechanisms underlying changes in spontaneous release of acetylcholine (ACh) induced by exogenous agonists and antagonists of endocannabinoid receptors were investigated by recording miniature endplate potentials (MEPPs) in motor synapses of mouse diaphragm preparations with intracellular microelectrodes. There have not been observed any statistically significant changes either in the membrane potential of muscle fibers or in the frequency, amplitude, and time parameters of the MEPPs under the action of AM-251 (1 μM), antagonist/inverse agonist of CB1 receptors, for 60 min. Activation of CB receptors by their exogenous agonist WIN 55,212-2 (WIN) (20 μM) for 1 h did not cause statistically significant changes in the amplitude of the MEPPs. However, MEPP frequency increased by more than 50% as compared to the control under the action of WIN for 30–60 min. Blocking of CB1 receptors by AM-251 (1 μM) prevented the WIN-induced increase in MEPP frequency. A protein kinase A inhibitor H-89 (1 μM) did not prevent the enhancement of the ACh secretion upon activation of CB receptors by WIN. WIN lost the ability to increase MEPP frequency in the presence of a phospholipase C inhibitor U73122 (5 μM), which did not affect by itself the amplitude and temporal characteristics or MEPP frequency. A protein kinase C inhibitor, chelerythrin (4 μM) or ryanodine, which blocks the ryanodine receptors (RyRs) at a concentration of 5 μM, also prevented the WIN-induced increase in MEPP frequency. Thus, a signaling cascade triggered by stimulation of presynaptic CB1 receptors with subsequent activation of phospholipase C, protein kinase C, and the release of stored calcium, leading to an increase in the frequency of spontaneous quantal release of ACh, has been detected for the first time in mouse motor synapses. This suggests the presence of CB1 receptors on the presynaptic membrane in mouse motor nerve terminals and the possibility of activation of these receptors by endocannabinoids for potentiating the spontaneous secretion of ACh.

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Физиология: биопотенциалы и электрическая активность клеток

2019 · BOOK · ru

Данное учебное пособие посвящено ознакомлению читателей с общими свойствами возбудимых клеток, к которым относятся нейроны, мышечные и рецепторные клетки человека и животных. Возбудимость означает способность клеток специфическим образом изменять электрический потенциал на мембране в ответ на внешние воздействия — генерировать так называемый потенциал действия. В пособии подробно рассмотрена физико-химическая природа электрических токов и потенциалов, существующих на мембране клеток в покоящемся состоянии (потенциал покоя) и при возбуждении (потенциал действия). Отдельные разделы посвящены описанию процессов передачи электрических сигналов от одной клетки к другой с помощью специализированных контактов — синапсов и возникающих там синаптических потенциалов. В дополнениях к главам представлены отдельные темы для более углубленного изучения и понимания материала. К каждой главе даны вопросы и задания для самопроверки знаний. Приведен список литературы, рекомендуемой для более полного ознакомления с предметом. В приложении дан тест для контроля усвоения материала

Regulation of Acetylcholine Quantal Release by Coupled Thrombin/BDNF Signaling in Mouse Motor Synapses

2019 · ARTICLE · en

The aim of this study was to compare the acute effects of thrombin and brain-derived neurotrophic factor (BDNF) on spontaneous miniature endplate potentials (MEPPs) and multiquantal evoked endplate potentials (EPPs) in mouse neuromuscular junctions (NMJs) of m. diaphragma and m. EDL. Intracellular microelectrode recordings of MEPPs and EPPs were used to evaluate the changes in acetylcholine (ACh) release in mature and newly-formed mouse NMJs. Thrombin (1 nM) increased the amplitude of MEPPs and EPPs by 25–30% in mature and newly-formed NMJs. This effect was due to an enhanced loading of synaptic vesicles with ACh and increase of ACh quantal size, since it was fully prevented by blocking of vesicular ACh transporter. It was also prevented by tropomyosin-related kinase B (TrkB) receptors inhibitor ANA12. Exogenous BDNF (1 nM) mimicked thrombin effect and increased the amplitude of MEPPs and EPPs by 25–30%. It required involvement of protein kinase A (PKA) and mitogen-activated protein kinase (MEK1/2)-mediated pathway, but not phospholipase C (PLC). Blocking A2A adenosine receptors by ZM241385 abolished the effect of BDNF, whereas additional stimulation of A2A receptors by CGS21680 increased MEPP amplitudes, which was prevented by MEK1/2 inhibitor U0126. At mature NMJs, BDNF enhanced MEPPs frequency by 30–40%. This effect was selectively prevented by inhibition of PLC, but not PKA or MEK1/2. It is suggested that interrelated effects of thrombin/BDNF in mature and newly-formed NMJs are realized via enhancement of vesicular ACh transport and quantal size increase. BDNF-induced potentiation of synaptic transmission involves the functional coupling between A2A receptor-dependent active PKA and neurotrophin-triggered MAPK pathway, as well as PLC-dependent increase in frequency of MEPPs.

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The Participation of Presynaptic Alpha7 Nicotinic Acetylcholine Receptors in the Inhibition of Acetylcholine Release during Long-Term Activity of Mouse Motor Synapses

2019 · ARTICLE · en

In the motor synapses of the mouse diaphragm, we recorded the miniature endplate potentials(MEPPs) and multiquantal endplate potentials induced by stimulation of the phrenic nerve (EPPs). Prolonged continuous rhythmic stimulation (50 Hz for 40 seconds) caused a depression of the synaptic transmission in the form of a gradual biphasic decrease in the quantal content of EPPs in the train. A rapid decrease in the quantal content of the EPPs to 50% of the amplitude of the first EPPs in the train (EPP1) during the first 10 seconds of activity was followed by a slower decrease in the EPP quantum content to 35–40% of EPP1 by the 40th second of stimulation. Blockage of the α7 nicotinic acetylcholine receptors by methyllycaconitine(20 nM), as well as ryanodine receptors by ryanodine (3 μM), or small-conductance calcium-activated potassium channels of the SK-type by apamin (1 μM) significantly reduced the development of depression; the EPP quantal content decreased to 65–70% of EPP1 by the 10th second of stimulation and maintained at this level for the next 30 seconds of stimulation. It was concluded that in mouse cholinergic motor synapses, the mechanism of transient depression of transmission may be autoinhibition of acetylcholine quantal secretion by endogenous acetylcholine/choline, which activates the α7 nicotinic acetylcholine receptors and triggers the signaling cascade that involves presynaptic ryanodine receptors and SK channels.

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Calcineurin and Its Role in Synaptic Transmission

2018 · ARTICLE · en

Calcineurin (CaN) is a serine/threonine phosphatase widely expressed in different cell types and structures including neurons and synapses. The most studied role of CaN is its involvement in the functioning of postsynaptic structures of central synapses. The role of CaN in the presynaptic structures of central and peripheral synapses is less understood, although it has generated a considerable interest and is a subject of a growing number of studies. The regulatory role of CaN in synaptic vesicle endocytosis in the synapse terminals is actively studied. In recent years, new targets of CaN have been identified and its role in the regulation of enzymes and neurotransmitter secretion in peripheral neuromuscular junctions has been revealed. CaN is the only phosphatase that requires calcium and calmodulin for activation. In this review, we present details of CaN molecular structure and give a detailed description of possible mechanisms of CaN activation involving calcium, enzymes, and endogenous and exogenous inhibitors. Known and newly discovered CaN targets at pre and postsynaptic levels are described. CaN activity in synaptic structures is discussed in terms of functional involvement of this phosphatase in synaptic transmission and neurotransmitter release.

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Курсы (2)