ХОЛИНЕРГИЧЕСКАЯ МОДУЛЯЦИЯ СЕКРЕЦИИ АЦЕТИЛХОЛИНА В НЕРВНО-МЫШЕЧНОМ СОЕДИНЕНИИ
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Ключевые слова

нервно-мышечное соединение
секреция ацетилхолина
никотиновый ионотропный холинорецептор
агонисты и антагонисты никотиновых холинорецепторов

Как цитировать

Бухараева, Э. А., & Скоринкин, А. И. (2021). ХОЛИНЕРГИЧЕСКАЯ МОДУЛЯЦИЯ СЕКРЕЦИИ АЦЕТИЛХОЛИНА В НЕРВНО-МЫШЕЧНОМ СОЕДИНЕНИИ. Российский физиологический журнал им. И. М. Сеченова, 107(4-5), 458–473. https://doi.org/10.31857/S0869813921040063

Аннотация

Влияние холинергических соединений (активаторов и блокаторов никотиновых холинорецепторов) на секрецию ацетилхолина из двигательных нервных окончаний представляет интерес в связи с вопросом о наличии механизма обратной связи в нервно-мышечном синапсе. Предполагается, что на нервных окончаниях могут быть ауторецепторы к ацетилхолину, изменение активности которых влияет на выделение медиатора в ответ на нервный стимул. Однако многочисленные экспериментальные данные не дают однозначного представления о направленности и механизмах действия как эндогенного ацетилхолина, так и других холинергических соединений на вызванную квантовую секрецию медиатора в нервно-мышечном синапсе. Актуальность таких исследований обусловлена необходимостью расшифровки эффектов этих соединений, так как многие из них применяются в клинической практике. Обзор посвящен анализу результатов исследований, проведенных на классических для нейрофизиологии объектах – нервно-мышечных препаратах теплокровных животных с помощью радиоизотопного метода оценки количества секретируемого из нервных окончаний медиатора и электрофизиологического метода определения числа квантов, выделяющихся в ответ на нервный стимул. Сопоставлены многочисленные данные, полученные при использовании активаторов и блокаторов ионотропных никотиновых рецепторов, а также вероятные механизмы действия холинергических соединений, модулирующих секреторный процесс. Предложена схема регуляции квантовой секреции, учитывающая новые сведения о возможном участии Шванновской клетки и о пресинаптической гомеостатической пластичности.

https://doi.org/10.31857/S0869813921040063
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Литература

Kamenskaya MA, Magazanik LG, Kotova ER, Samybaldina NK, Miroshnikov AI, Apsalon UR (1979) Effect of presynaptic neurotoxins from bee and cobra venom on spontaneous mediator secretion from mouse motor-nerve ending. Bull Exp Biol Med 87(5):402–405. https://doi.org/10.1007/BF00806665

Magazanik LG, Nikol'skiĭ EE (1979) Pre- and postsynaptic action of a cholinomimetic (subecholine) under a voltage clamp of the postsynaptic membrane. Dokl Akad Nauk SSSR 249(6):1488–1491.

Magazanik LG, Potapjeva NN, Fedorova IM (1998) Modulation of transmitter release from motor nerve endings by muscarinic and adenosine receptors. J Neurochem 71:S4.

Nikolsky EE, Vyskocil F, Bukharaeva EA, Samigullin D, Magazanik LG (2004) Cholinergic regulation of the evoked quantal release at frog neuromuscular junction. J Physiol 560:77–88. https://doi.org/10.1113/jphysiol.2004.065805.4

Bukharaeva EA, Samigullin D, Nikolsky EE, Magazanik LG (2007) Modulation of the kinetics of evoked quantal release at mouse neuromuscular junctions by calcium and strontium. J Neurochem 100(4):939–949. https://doi.org/10.1111/j.1471-4159.2006.04282.x

Santafé MM, Salon I, Garcia N, Lanuza MA, Uchitel OD, Tomàs J (2003) Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult rat. Eur J Neurosci 17(1):119–127. https://doi.org/10.1046/j.1460-9568.2003.02428.x

Khaziev EF, Fatikhov NF, Samigullin DV, Barrett GL, Bukharaeva EA, Nikolsky EE (2012) Decreased entry of calcium into motor nerve endings upon activation of presynaptic cholinergic receptors. Dokl Biol Sci 446: 283–285. https://doi.org/10.1134/S0012496612050080

Connor EA, Dunaevsky A, Griffiths DJ, Hardwick JC, Parsons RL (1997) Transmitter release differs at snake twitch and tonic endplates during potassium-induced nerve terminal depolarization. J Neurophysiol 77(2): 749–760. https://doi.org/10.1152/jn.1997.77.2.749

Foldes FF, Chaudhry IA, Kinjo M, Nagashima H (1989) Inhibition of mobilization of acetylcholine: the weak link in neuromuscular transmission during partial neuromuscular block with d-tubocurarine. Anesthesiology 71: 218–223.

Somogyi GT, Vizi ES, Chaudhry IA, Nagashima H, Duncalf D, Foldes FF, Goldiner PL. (1987) Modulation of stimulation-evoked release of newly formed acetylcholine from mouse hemidiaphragm preparation. Naunyn Schmiedebergs Arch Pharmacol 336(1):11–15. doi: 10.1007/BF00177744

Katz B, Miledi R (1979) Estimates of quantal content during 'chemical potentiation' of transmitter release Proc R Soc Lond B Biol Sci 205(1160):369–378. https://doi.org/10.1098/rspb.1979.0070

Li RA, Ennis IL, Vélez P, Tomaselli GF, Marbán E (2000) Novel structural determinants of mu-conotoxin (GIIIB) block in rat skeletal muscle (mu1) Na+channels. J Biol Chem 275(36): 27551–27558. http://dx.doi.org/10.1074/jbc.M909719199

Wessler I, Halank M, Rasbach J, Kitbinger H (1986) Presynaptic nicotine receptors mediating a positive feed-back on transmitter release from the rat phrenic nerve. Naunyn-Schmiedebergs Arch Pharmacol 334: 365–372. https://doi.org/10.1007/BF00569371

Wessler I, Apel C, Garmsen M, Klein A (1992) Effects of nicotine receptor agonists on acetylcholine release from the isolated motor nerve, small intestine and trachea of rats and guinea-pigs. Clin Investig 70(3-4): 182–189. https://doi.org/10.1007/BF00184649

Wessler I, Scheuer B, Kilbinger H (1987) [3H]acetylcholine release from the phrenic nerve is increased or decreased by activation or desensitization of nicotine receptors. Eur J Pharmacol 135(1):85–87. https://doi.org/10.1016/0014-2999(87)90760-6

Giniatullin RA, Magazanik LG (1998) Does desensitisation of acetylcholine receptors play a physiological role in the neuromuscular synapse? Ross Fiziol Zh Im I M Sechenova 84(1-2): 3–14.

Wilson DF (1982) Influence of presynaptic receptors on neuromuscular transmission in rat. Am J Physiol 242(5): 366–372. https://doi.org/10.1152/ajpcell.1982.242.5.C366

Prior C., Dempster J, Marshall IG (1993) Electrophysiological analysis of transmission at the skeletal neuromuscular junction. J Pharmacol Toxicol Met 30: 1–17. https://doi.org/10.1016/1056-8719(93)90002-V

Prior C, Singh S (2000) Factors influencing the low-frequency associated nicotinic ACh autoreceptor-mediated depression of ACh release from rat motor nerve terminals. Br J Pharmacol 129(6): 1067–1074. https://doi.org/10.1038/sj.bjp.0707442

Singh S, Prior C (1998) Prejunctional effects of the nicotinic ACh receptor agonist dimethylphenylpiperazinium at the rat neuromuscular junction. J Physiol 511: 451–560. https://doi.org/10.1111/j.1469-7793.1998.451bh.x

Balezina OP, Fedorin VV, Gaidukov AE (2006) Effect of nicotine on neuromuscular transmission in mouse motor synapses. Bull Exp Biol Med 142(1): 17–21. doi: 10.1007/s10517-006-0280-32006

Gaydukov AE, Bogacheva PO, Tarasova EO, Balezina OP (2014) The mechanism of choline-mediated inhibition of acetylcholine release in mouse motor synapses. Acta Naturae 6(4): 110–115. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4273098/pdf/AN20758251-23-110.pdf

Apel C, Rícný J, Wagner C, Wessler I (1995) alpha-Bungarotoxin, kappa-bungarotoxin, alpha-cobratoxin and erabutoxin-b do not affect [3H]acetylcholine release from the rat isolated left hemidiaphragm. Naunyn Schmiedebergs Arch Pharmacol 352(6): 646–652. https://doi.org/10.1007/BF00171324

Vizi ES, Chaudhry IA, Goldiner PL, Ohta Y, Nagashima H, Foldes FF (1991) The pre- and postjunctional components of the neuromuscular effect of antibiotics. J Anesth 5(1): 1–9. https://doi.org/10.1007/s0054010050001

Vizi ES, Somogyi GT, Nagashima H, Duncalf D, Chaudhry IA, Kobayashi O, Goldiner PL, Foldes FF (1987) Tubocurarine and pancuronium inhibit evoked release of acetylcholine from the mouse hemidiaphragm preparation. Br J Anaesth 59(2): 226–231. https://doi.org/10.1093/bja/59.2.226

Faria M, Oliveira L, Timoteo MA, Lobo MG, Correia-De-Sa P (2003) Blockade of neuronal facilitatory nicotinic receptors containing alpha 3 beta 2 subunits contribute to tetanic fade in the rat isolated diaphragm. Synapse 49: 77–88 https://doi.org/10.1002/syn.10211

Vizi ES, Somogyi GT (1989) Prejunctional modulation of acetylcholine release from the skeletal neuromuscular junction: link between positive (nicotinic)-and negative (muscarinic)-feedback modulation. Br J Pharmacol 97(1): 65–70. https://doi.org/10.1111/j.1476-5381.1989.tb11924.x

Wessler I (1992) Acetylcholine at motor nerves: storage, release, and presynaptic modulation by autoreceptors and adrenoceptors. Int Rev Neurobiol 34: 283–384. doi: 10.1016/s0074-7742(08)60100-2

Kimura I, Okazaki M, Uwano T, Kobayashi S, Kimura M (1991) Succinylcholine-induced acceleration and suppression of electrically evoked acetylcholine release from mouse phrenic nerve-hemidiaphragm muscle preparation. Jpn J Pharmacol 57(3): 397–403. https://doi.org/10.1254/jjp.57.397

Tian L, Prior C, Dempster J, Marshall IG (1994) Nicotinic antagonist-produced frequency-dependent changes in acetylcholine release from rat motor nerve terminals. J Physiol 476(3): 517–529. https://doi.org/10.1113/jphysiol.1994.sp020151

Ferry CB, Kelly SS (1988) The nature of the presynaptic effects of (+)-tubocurarine at the mouse neuromuscular junction. J Physiol 403: 425–437. https://doi.org/10.1113/jphysiol.1988.sp017257

Wilson DF (1982) Influence of presynaptic receptors on neuromuscular transmission in rat. Am J Physiol 242: 366–373. https://doi.org/10.1152/ajpcell.1982.242.5.C366

Wilson DF, Thomsen RH (1991) Nicotinic receptors on the rat phrenic nerve: evidence for negative feedback. Neurosci Lett 132(2): 163–166. https://doi.org/10.1016/0304-3940(91)90292-2

Tian L, Prior C, Dempster J, Marshall IG. (1997) Hexamethonium- and methyllycaconitine-induced changes in acetylcholine release from rat motor nerve terminals. Br J Pharmacol 122(6):1025–1034. https://doi.org/10.1038/sj.bjp.0701481

Wilson DF, Thomsen RH (1992) Effects of hexamethonium on transmitter release from the rat phrenic nerve. Neurosci Lett 143(1-2): 79–82. https://doi.org/10.1016/0304-3940(92)90237-2

Wilson DF, West AE, Lin Y (1995) Inhibitory action of nicotinic antagonists on transmitter release at the neuromuscular junction of the rat. Neurosci Lett 186(1): 29–32. https://doi.org/10.1016/0304-3940(95)11274-Z

Domet MA, Webb CE, Wilson DF (1995) Impact of alpha-bungarotoxin on transmitter release at the neuromuscular junction of the rat. Neurosci Lett 199(1): 49–52. https://doi.org/10.1016/0304-3940(95)12013-t

Prior C, Tian L, Dempster J, Marshall IG (1995) Prejunctional actions of muscle relaxants: Synaptic vesicles and transmitter mobilization as sites of action. Gen Pharmacol 26: 659–666. https://doi.org/10.1016/0306-3623(94)00246-j

Bowman WC, Prior C, Marshall IG (1990) Presynaptic Receptors in the Neuromuscular Junction. Ann N Y Acad Sci 604: 69–81. https://doi.org/10.1111/j.1749-6632.1990.tb31983.x

Bowman WC, Marshall LG, Gibb AG, Harbome AJ (1988) Feedback control of transmitter release at the neuromuscular junction. Trends Pharmacol Sci 9: 16–20.

Jones W, Salpeter M (1983) Absence of [125I] alpha-bungarotoxin binding to motor nerve terminals of frog, lizard and mouse muscle. J Neurosci 3(2): 326–331. https://doi.org/10.1523/JNEUROSCI.03-02-00326

Tsuneki H, Kimura I, Dezaki K, Kimura M, Sala C, Fumagalli G (1995) Immunohistochemical localization of neuronal nicotinic receptor subtypes at the pre- and postjunctional sites in mouse diaphragm muscle. Neurosci Lett 196: 13–16. https://doi.org/10.1016/0304-3940(95)11824-G

Petrov KA, Girard E, Nikitashina AD, Colasante C, Bernard V, Nurullin L, Leroy J, Samigullin D, Colak O, Nikolsky E, Plaud B, Krejci E (2014) Schwann cells sense and control acetylcholine spillover at the neuromuscular junction by α7 nicotinic receptors and butyrylcholinesterase. J Neurosci 34(36): 11870–11883. https://doi.org/10.1523/JNEUROSCI.0329-14.2014

Fagerlund MJ, Eriksson LI (2009) Current concepts in neuromuscular transmission. Br J Anaesth 103(1): 108–114. https://doi.org/10.1093/bja/aep150

Jonsson M, Gurley D, Dabrowski M, Larsson O, Johnson EC, Eriksson LI (2006) Distinct pharmacologic properties of neuromuscular blocking agents on human neuronal nicotinic acetylcholine receptors: a possible explanation for the train-of-four fade. Anesthesiology 105(3): 521–533. https://doi.org/10.1097/00000542-200609000-00016

Wessler I (1989) Control of transmitter release from the motor nerve by presynaptic nicotinic and muscarinic autoreceptors. Trends Pharmacol Sci 10(3): 110–114. https://doi.org/10.1016/0165-6147(89)90208-3

Vizi ES, Kiss J, Elenkov IJ (1991) Presynaptic modulation of cholinergic and noradrenergic neurotransmission: interaction between them. NIPS 6: 119– 123.

Miledi R, Molenaar PC, Polak RL (1978) Alpha-Bungarotoxin enhances transmitter "released" at the neuromuscular junction. Nature 272(5654): 641–643. https://doi.org/10.1038/272641a0

Kabbani N, Nichols RA (2018) Beyond the Channel: Metabotropic Signaling by Nicotinic Receptors. Trends Pharmacol Sci 39(4): 354–366. https://doi.org/10.1016/j.tips.2018.01.002

Tsuneki H, Klink R, Léna C, Korn H, Changeux JP (2000) Calcium mobilization elicited by two types of nicotinic acetylcholine receptors in mouse substantia nigra pars compacta. Eur J Neurosci 12(7): 2475–2485. https://doi.org/10.1046/j.1460-9568.2000.00138.x

Djemil S, Chen X, Zhang Z, Lee I, Rauf M, Pak D, Dzakpasu R (2020) Activation of nicotinic acetylcholine receptors induces potentiation and synchronization within in vitro hippocampal networks. J Neurochem. 153(4): 468–484. https://doi.org/10.1111/jnc.14938

Mukhamedyarov M, Kochunova J, Yusupova E (2010) The contribution of calcium/calmodulin-dependent protein-kinase II (CaMKII) to short-term plasticity at the neuro-muscular junction. Brain Res Bull 81(6): 613–616. https://doi.org/10.1016/j.brainresbull.2009.12.010

Kulak JM, McIntosh JM, Yoshikami D, Olivera BM (2001) Nicotine-evoked transmitter release from synaptosomes: functional association of specific presynaptic acetylcholine receptors and voltage-gated calcium channels. J Neurochem 77(6): 1581–1589. https://doi.org/10.1046/j.1471-4159.2001.00357.x

Bowman WC (1989) Presynaptic nicotinic autoreceptors. Trends Pharmacol Sci. 10(4): 136–137. doi: 10.1016/0165-6147(89)90162-4

Tarasova EO, Gaydukov AE, Balezina OP (2015) Methods of activation and the role of calcium/calmodulin-dependent protein kinase II in the regulation of acetylcholine secretion in the motor synapses of mice. Neurochem J 9(2): 101–107 https://doi.org/10.1134/S1819712415020099

Gaydukov AE, Balezina OP (2017) CaMKII Is Involved in the Choline-Induced Downregulation of Acetylcholine Release in Mouse Motor Synapses. Acta Naturae 9(4): 110–113

Gaydukov AE, Bogacheva PO, Balezina OP (2019) The Participation of Presynaptic Alpha7 Nicotinic Acetylcholine Receptors in the Inhibition of Acetylcholine Release during Long-Term Activity of Mouse Motor Synapses. Neurochem J 13(1): 20–27. https://doi.org/10.1134/S1819712419010082

Shen JX, Yakel JL (2009) Nicotinic acetylcholine receptor-mediated calcium signaling in the nervous system. Acta Pharmacol Sin 30(6):673–680. https://doi.org/10.1038/aps.2009.64

King JR, Ullah A, Bak E, Jafri MS, Kabbani N (2018) Ionotropic and metabotropic mechanisms of allosteric modulation of α7 nicotinic receptor intracellular calcium. Mol Pharmacol 93: 601–611. https://doi.org/10.1124/mol.117.111401

Penner R, Dreyer F (1986) Two different presynaptic calcium currents in mouse motor nerve terminals. Pfugers Arch 406: 190–197. https://doi.org/10.1007/BF00586682

Wood SJ, Slater CR (2001) Safety factor at the neuromuscular junction. Prog Neurobiol 64(4): 393–429. doi: 10.1016/s0301-0082(00)00055-1

Zhangsun D, Zhu X, Wu Y, Hu Y, Kaas Q, Craik DJ, McIntosh JM, Luo S (2015). Key residues in the nicotinic acetylcholine receptor β2 subunit contribute to α-conotoxin LvIA binding. J Biol Chem 290(15): 9855–9862. doi: 10.1074/jbc.M114.632646

Petrov KA, Malomouzh AI, Kovyazina IV, Krejci E, Nikitashina AD, Proskurina SE, Zobov VV, Nikolsky EE (2013) Regulation of acetylcholinesterase activity by nitric oxide in rat neuromuscular junction via N-methyl-D-aspartate receptor activation. Eur J Neurosci 37(2): 181–189. https://doi.org/10.1111/ejn.12029

Noronha-Matos JB, Oliveira L, Peixoto A, Almeida L, Castellão-Santana ML, Ambiel CR, Alves-do Prado W, Correia-de-Sá P (2020) Nicotinic α7 receptor-induced adenosine release from perisynaptic Schwann cells controls acetylcholine spillover from motor endplates. J Neurochem 154(3): 263–283. https://doi.org/10.1111/jnc.14975.

Correia-de-Sá P, Sebastião AM, Ribeiro JA (1991) Inhibitory and excitatory effects of adenosine receptor agonists on evoked transmitter release from phrenic nerve ending of the rat. Br J Pharmacol 103: 1614–1620. https://doi.org/10.1111/j.1476-5381.1991.tb09836.x

Wang X, McIntosh JM, Rich MM (2018) Muscle Nicotinic Acetylcholine Receptors May Mediate Trans-Synaptic Signaling at the Mouse Neuromuscular Junction. J Neurosci 38(7): 1725-1736. https://doi.org/10.1523/JNEUROSCI.1789-17.2018