РЕМОДЕЛИРОВАНИЕ ВНЕКЛЕТОЧНО РЕГИСТРИРУЕМЫХ ПОТЕНЦИАЛОВ ДЕЙСТВИЯ КАРДИОМИОЦИТОВ СУБЭПИКАРДА СЕРДЦА КРЫСЫ ПОСЛЕ ИШЕМИЧЕСКИ-РЕПЕРФУЗИОННОГО ПОВРЕЖДЕНИЯ
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Ключевые слова

миокард
ишемия
реперфузия
кардиомиоциты
внеклеточный потенциал действия
Т-система

Аннотация

Известно, что ряд системных сердечных заболеваний различной этиологии (хроническая ишемия, аортальный стеноз, гипертензия, диабетическая кардиомиопатия, реперфузионное повреждение после ишемии и др.), ведущих к развитию сердечной недостаточности, сопровождается выраженной реорганизацией Т-системы кардиомиоцитов как у человека, так и у животных. Однако изменения в электрогенезе клеточной мембраны Т-системы кардиомиоцитов при этих заболеваниях практически не изучены. Целью работы было выяснить динамику изменений электрогенеза различных отделов мембраны кардиомиоцитов субэпикарда на разных сроках после ишемии-реперфузии (ИР) левого желудочка (ЛЖ) у крыс с использованием метода внеклеточной регистрации и оценить морфологические изменения Т-системы с использованием конфокальной микроскопии. Исследование проводили через один день, две и четыре недели после ИР. Было установлено, что сразу после ИР наблюдается изменение внеклеточно регистрируемых потенциалов действия первого типа (вПД1, характеризующиеся одним негативным пиком), регистрируемых в зоне мембраны кардиомиоцитов субэпикарда, свободной от входов в t-трубочки. Начиная с 24 часов, вплоть до четырёх недель после ИР происходило увеличение длительности времени спада (T90) и частоты встречаемости фазы следовой гиперполяризации вПД1, достигающих максимальных значений к четырём неделям после ИР. Помимо этого, в течение четырёх недель после ИР отмечается выраженное снижение амплитуды второго пика внеклеточно регистрируемых потенциалов действия второго типа (вПД2, характеризующиеся наличием двух негативных пиков), регистрируемых в зоне мембраны кардиомиоцитов субэпикарда, имеющей входы t-трубочек. Однако изменений в структурной организации Т-системы обнаружено не было. Эти данные свидетельствуют о том, что функциональные модификации Т-системы эпикардиальных кардиомиоцитов после ИР могут предшествовать их структурным модификациям.

https://doi.org/10.31857/S004445292305008X
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Литература

Reimer KA, Lowe JE, Rasmussen MM, Jennings RB (1977) The wavefront phenomenon of ischemic cell death. 1. Myocardial infarct size vs duration of coronary occlusion in dogs. Circulation 56:786–794. https://doi.org/10.1161/01.CIR.56.5.786

Boatwright RB, Downey HF, Bashour FA, Crystal GJ (1980) Transmural variation in autoregulation of coronary blood flow in hyperperfused canine myocardium. Circ Res 47:599–609. https://doi.org/10.1161/01.RES.47.4.599

Christia P, Bujak M, Gonzalez-Quesada C, Chen W, Dobaczewski M, Reddy A, Frangogiannis NG (2013) Systematic characterization of myocardial inflammation, repair, and remodeling in a mouse model of reperfused myocardial infarction. J Histochem Cytochem 61:555–570. https://doi.org/10.1369/0022155413493912

Reed GW, Rossi JE, Cannon CP (2017) Acute myocardial infarction. Lancet 389:197–210. https://doi.org/10.1016/S0140-6736(16)30677-8

Lindsey ML, Bolli R, Canty JM, Du XJ, Frangogiannis NG, Frantz S, Gourdie RG, Holmes JW, Jones SP, Kloner RA, Lefer DJ, Liao R, Murphy E, Ping P, Przyklenk K, Recchia FA, Longacre LS, Ripplinger CM, Van Eyk JE, Heusch G (2018) Guidelines for experimental models of myocardial ischemia and infarction. Am J Physiol Heart Circ Physiol 314:H812–H838. https://doi.org/10.1152/ajpheart.00335.2017

Yeap XY, Dehn S, Adelman J, Lipsitz J, Thorp EB (2013) Quantitation of acute necrosis after experimental myocardial infarction. Methods Mol Biol 1004:115–133. https://doi.org/10.1007/978-1-62703-383-1_9

Liu T, Howarth AG, Chen Y, Nair AR, Yang HJ, Ren D, Tang R, Sykes J, Kovacs MS, Dey D, Slomka P, Wood JC, Finney R, Zeng M, Prato FS, Francis J, Berman DS, Shah PK, Kumar A, Dharmakumar R (2022) Intramyocardial Hemorrhage and the "Wave Front" of Reperfusion Injury Compromising Myocardial Salvage. J Am Coll Cardiol 79:35–48. https://doi.org/10.1016/j.jacc.2021.10.034

Frantz S, Hundertmark MJ, Schulz-Menger J, Bengel FM, Bauersachs J (2022) Left ventricular remodelling post-myocardial infarction: pathophysiology, imaging, and novel therapies. Eur Heart J 43:2549-2561. https://doi.org/10.1093/eurheartj/ehac223

Wei S, Guo A, Chen B, Kutschke W, Xie YP, Zimmerman K, Weiss RM, Anderson ME, Cheng H, Song LS (2010) T-tubule remodeling during transition from hypertrophy to heart failure. Circ Res 107:520–531. https://doi.org/10.1161/CIRCRESAHA.109.212324

Xie YP, Chen B, Sanders P, Guo A, Li Y, Zimmerman K, Wang LC, Weiss RM, Grumbach IM, Anderson ME, Song LS (2012) Sildenafil prevents and reverses transverse-tubule remodeling and Ca2+ handling dysfunction in right ventricle failure induced by pulmonary artery hypertension. Hypertension 59:355–362. https://doi.org/10.1161/HYPERTENSIONAHA.111.180968

Ibrahim M, Gorelik J, Yacoub MH, Terracciano CM (2011) The structure and function of cardiac t-tubules in health and disease. Proc Biol Sci 278:2714–2723. https://doi.org/10.1098/rspb.2011.0624

Ibrahim M, Terracciano CM (2013) Reversibility of T-tubule remodelling in heart failure: Mechanical load as a dynamic regulator of the T-tubules. Cardiovasc Res 98:225–232. https://doi.org/10.1093/cvr/cvt016

Louch WE, Sejersted OM, Swift F (2010) There goes the neighborhood: Pathological alterations in T-tubule morphology and consequences for cardiomyocyte Ca2+ handling. J Biomed Biotechnol 2010:503906. https://doi.org/10.1155/2010/503906

Wang S, Zhou Y, Luo Y, Kan R, Chen J, Xuan H, Wang C, Chen J, Xu T, Li D (2021) SERCA2a ameliorates cardiomyocyte T-tubule remodeling via the calpain/JPH2 pathway to improve cardiac function in myocardial ischemia/reperfusion mice. Sci Rep 11:2037. https://doi.org/10.1038/s41598-021-81570-4

Кубасов ИВ, Чистякова ОВ, Сухов ИБ, Панов АА, Добрецов МГ (2020) Изменения внеклеточно регистрируемых потенциалов действия изолированного сердца крысы при развитии стрептозотоцинового диабета. Рос физиол журн им ИМ Сеченова 106:1266–1277. [Kubasov IV, Chistyakova OV, Sukhov IB, Panov AA, Dobretsov MG (2020) Functional changes in the T-system of cardiomyocytes of the isolated rat heart during development of streptozotocin-induced diabetes. Russ J Physiol 106:1266–1277. (In Russ)]. https://doi.org/10.31857/s0869813920100052

Kubasov IV, Bobkov DE, Stepanov AV, Sukhov IB, Chistyakova OV, Dobretsov MG (2020) Evaluation of the T-System of Rat Cardiomyocytes during Early Stages of Streptozotocin-Induced Diabetes. Russian Journal of Physiology 106:1098–1108. https://doi.org/10.31857/S0869813920090046

Swift F, Franzini-Armstrong C, Øyehaug L, Enger UH, Andersson KB, Christensen G, Sejersted OM, Louch WE (2012) Extreme Sarcoplasmic Reticulum Volume Loss and Compensatory T-Tubule Remodeling after Serca2 Knockout. Proc Natl Acad Sci USA 109:3997–4001. https://doi.org/10.1073/pnas.1120172109

Pinali C, Bennett H, Davenport JB, Trafford AW, Kitmitto A (2013) Three-Dimensional Reconstruction of Cardiac Sarcoplasmic Reticulum Reveals a Continuous Network Linking Transverse-Tubules: This Organization Is Perturbed in Heart Failure. Circ Res 113:1219–1230. https://doi.org/10.1161/CIRCRESAHA.113.301348

Knollmann BC, Tranquillo J, Sirenko SG, Henriquez C, Franz MR (2002) Microelectrode study of the genesis of the monophasic action potential by contact electrode technique. J Cardiovasc Electrophysiol 13:1246–1252. https://doi.org/10.1046/j.1540-8167.2002.01246.x

Kondo M, Nesterenko V, Antzelevitch C (2004) Cellular basis for the monophasic action potential. Which electrode is the recording electrode? Cardiovasc Res 63:635–644. https://doi.org/10.1016/j.cardiores.2004.05.003

Knollmann BC, Schober T, Petersen AO, Sirenko SG, Franz MR (2007) Action potential characterization in intact mouse heart: steady-state cycle length dependence and electrical restitution. Am J Physiol Heart Circ Physiol 292:H614–621. https://doi.org/10.1152/ajpheart.01085.2005

Kubasov IV, Dobretsov M (2012) Two types of extracellular action potentials recorded with narrow-tipped pipettes in skeletal muscle of frog, Rana temporaria. J Physiol 590:2937–2944. https://doi.org/10.1113/jphysiol.2012.230813

Kubasov IV, Stepanov AV, Györke S (2017) Action potential heterogeneity as revealed by extracellular microelectrode recording from the surface of the isolated rat heart. J Evol Biochem Phys 53:515–518. https://doi.org/10.1134/S0022093017060102

Kubasov IV, Stepanov A, Bobkov D, Radwanski PB, Terpilowski MA, Dobretsov M, Gyorke S (2018) Sub-cellular Electrical Heterogeneity Revealed by Loose Patch Recording Reflects Differential Localization of Sarcolemmal Ion Channels in Intact Rat. Front Physiol 9:61. https://doi.org/10.3389/fphys.2018.00061

Ciuffreda MC, Tolva V, Casana R, Gnecchi M, Vanoli E, Spazzolini C, Roughan J, Calvillo L (2014) Rat Experimental Model of Myocardial Ischemia/Reperfusion Injury: An Ethical Approach to Set Up the Analgesic Management of Acute Post-Surgical Pain. PLoS One 9:e95913. https://doi.org/10.1371/journal.pone.0095913

Murakami M, Niwa H, Kushikata T, Watanabe H, Hirota K, Ono K, Ohba T (2014) Inhalation anesthesia is preferable for recording rat cardiac function using an electrocardiogram. Biol Pharm Bull 37:834–839. https://doi.org/10.1248/bpb.b14-00012

Zhang R, Han D, Li Z, Shen C, Zhang Y, Li J, Yan G, Li S, Hu B, Li J, Liu P (2018) Ginkgolide C alleviates myocardial ischemia/reperfusion-induced inflammatory injury via inhibition of CD40-NF-κB pathway. Front Pharmacol 9:109. https://doi.org/10.3389/fphar.2018.00109

Fishbein MC, Meerbaum S, Rit J, Lando U, Kanmatsuse K, Mercier JC, Corday E, Ganz W (1981) Early phase acute myocardial infarct size quantification: validation of the triphenyl tetrazolium chloride tissue enzyme staining technique. Am Heart J 101:593–600. https://doi.org/10.1016/0002-8703(81)90226-X

Kubasov IV, Dobretsov MG, Bobkov DE, Panov AA (2020) A Putative Relationship between Polymorphism of Extracellularly Recorded Action Potentials and Organization of the T-tubular System in Rat Ventricular and Atrial Cardiomyocytes. J Evol Biochem Phys 56:333–337. https://doi.org/10.1134/S0022093020040043

Kubasov IV, Stepanov AV, Panov AA, Chistyakova OV, Sukhov IB, Dobretsov MG (2021) Role of Potassium Currents in the Formation of After-Hyperpolarization Phase of Extracellular Action Potentials Recorded from the Control and Diabetic Rat Heart Ventricular Myocytes. J Evol Biochem Phys 57:1511–1521. https://doi.org/10.1134/S0022093021060272

Tejada T, Tan L, Torres RA, Calvert JW, Lambert JP, Zaidi M, Husain M, Berce MD, Naib H, Pejler G, Abrink M, Graham RM, Lefer DJ, Naqvi N, Husain A (2016) IGF-1 degradation by mouse mast cell protease 4 promotes cell death and adverse cardiac remodeling days after a myocardial infarction. Proc Natl Acad Sci U S A 113:6949–6954. https://doi.org/10.1073/pnas.1603127113

Shimizu Y, Nicholson CK, Lambert JP, Barr LA, Kuek N, Herszenhaut D, Tan L, Murohara T, Hansen JM, Husain A, Naqvi N, Calvert JW (2016) Sodium sulfide attenuates ischemic-induced heart failure by enhancing proteasomal function in an Nrf2-dependent manner. Circ Heart Fail 9:e002368. https://doi.org/10.1161/CIRCHEARTFAILURE.115.002368

Fishbein MC, Maclean D, Maroko PR (1978) Experimental myocardial infarction in the rat: qualitative and quantitative changes during pathologic evolution. Am J Pathol 90:57–70.

Chrastina A, Pokreisz P, Schnitzer JE (2014) Experimental model of transthoracic, vascular-targeted, photodynamically induced myocardial infarction. Am J Physiol Heart Circ Physiol 306:H270–H278. https://doi.org/10.1152/ajpheart.00818.2012

Speechly-Dick ME, Mocanu MM, Yellon DM (1994) Protein kinase C. Its role in ischemic preconditioning in the rat. Circ Res 75:586–590. https://doi.org/10.1161/01.RES.75.3.586

Konopelski P, Ufnal M (2016) Electrocardiography in rats: a comparison to human. Physiol Res 65:717–725. https://doi.org/10.33549/physiolres.933270

Normann SJ, Priest RE, Benditt EP (1961) Electrocardiogram in the normal rat and its alteration with experimental coronary occlusion. Circ Res 9:282–287. https://doi.org/10.1161/01.RES.9.2.282

Brette F, Orchard C (2003) T-Tubule Function in Mammalian Cardiac Myocytes. Circ Res 92:1182–1192. https://doi.org/10.1161/01.RES.0000074908.17214.FD

Hong TT, Shaw RM (2017) Cardiac T-tubule microanatomy and function. Physiol Rev 97:227–252. https://doi.org/10.1152/physrev.00037.2015

Jourdon P, Feuvray D (1993) Calcium and potassium currents in ventricular myocytes isolated from diabetic rats. J Physiol 470:411–429. https://doi.org/10.1113/jphysiol.1993.sp019866

Shimoni Y, Ewart HS, Severson D (1999) Insulin stimulation of rat ventricular K+ currents depends on the integrity of the cytoskeleton. J Physiol 514:735–745. https://doi.org/10.1111/j.1469-7793.1999.735ad.x

Brouillette J, Clark RB, Giles WR, Fiset C (2004) Functional properties of K+ currents in adult mouse ventricular myocytes. J Physiol 559:777–798. https://doi.org/10.1113/jphysiol.2004.063446

Chang PC, Turker I, Lopshire JC, Masroor S, Nguyen BL, Tao W, Rubart M, Chen PS, Chen Z, Ai T (2013) Heterogeneous upregulation of apamin-sensitive potassium currents in failing human ventricles. J Am Heart Assoc 2:e004713. https://doi.org/10.1161/JAHA.112.004713

Chua SK, Chang PC, Maruyama M, Turker I, Shinohara T, Shen MJ, Chen Z, Shen C, Rubart-von der Lohe M, Lopshire JC, Ogawa M, Weiss JN, Lin SF, Ai T, Chen PS (2011) Small conductance calcium-activated potassium channel and recurrent ventricular fibrillation in failing rabbit ventricles. Circ Res 108:971–979. https://doi.org/10.1161/CIRCRESAHA.110.238386

Gui L, Bao Z, Jia Y, Qin X, Cheng ZJ, Zhu J, Chen QH (2013) Ventricular tachyarrhythmias in rats with acute myocardial infarction involves activation of small-conductance Ca2+-activated K+ channels. Am J Physiol Heart Circ Physiol 304:H118–H130. https://doi.org/10.1152/ajpheart.00820.2011

Bonilla IM, Long VP III, Vargas-Pinto P, Wright P, Belevych A, Lou Q, Mowrey K, Yoo J, Binkley PF, Fedorov VV, Györke S, Janssen PML, Kilic A, Mohler PJ, Carnes CA (2014) Calcium-Activated Potassium Current Modulates Ventricular Repolarization in Chronic Heart Failure. PLoS ONE 9: e108824. https://doi.org/10.1371/journal.pone.0108824