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Effect of Aerobic Exercise on Left Ventricular Connexin43 Expression and Distribution in Juvenile and Young Adult Rats

1Universitas Brawijaya, Indonesia

2Universitas Indonesia, Indonesia

Received: 26 Mar 2021; Revised: 27 Apr 2021; Accepted: 26 Apr 2021; Available online: 30 Apr 2021; Published: 30 Apr 2021.
Open Access Copyright (c) 2021 Journal of Biomedicine and Translational Research

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Background: Gap Junction (GJ) plays a role in supporting the heart electricity. Connexin43 (Cx43) as the main protein constituent of GJ in left cardiac ventricle, will increase in number and slightly redistributed to the lateral sides of cardiomyocytes after aerobic exercise in adulthood. The effects of aerobic exercise that begin at childhood are not well known.

Objective: This study aims to observe the effect of aerobic exercise which started from childhood on left ventricle Cx43 distribution.

Methods: This study was conducted on 28 male Juvenile (4 weeks) and young adult (8 weeks) rats, divided into 7 groups: 1) Juvenile rats undergoing 4 weeks of exercise (E-J4); 2) Control E-J4 (C-J4); 3) Juvenile rats undergoing 8 weeks of exercise (E-J8); 4) Control EJ-8 (C-J8); 5) Juvenile rats undergoing 12 weeks of exercise (E-J12; 6); Young adult rats undergoing 8 weeks of exercise (E-Yo8); 7) Control E-J12 and E-Yo8 (C-JY128). Exercise group will undergo different length of duration, starting from week 4 until 12 weeks. Cx43 was identified by immunohistochemical staining and analyzed with ImageJ software. Comparison was analyzed using independent t-test.

Results: Insignificant lower of total Cx43 expression in E-J4 (64200.45 + 4243.676 total area, p >0.05) compared to control. In contrast, a significant higher of total Cx43 expression was observed in EJ-8, EJ-12 and E-Yo8 (80152.95 + 3760.481, p = 0.001; 75596.775 + 3976.333, p = 0,002; 81216.85+ 2475.768, p = 0,000). Slightly higher of lateral Cx43 redistribution occurred in all aerobic exercise, with significant lateralization in E-J8 and E-Yo8.

Conclusion: Aerobic exercise increases Cx43 and slightly redistributed to lateral myocytes under normal condition both in juvenile and young adult rats.

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Keywords: Aerobic exercise; left ventricle; connexin43; juvenile; young adult

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  1. Fallis A. Global Recommendations on Physical activity for Health (WHO). J Chem Inf Model. 2013;53(9)
  2. Pate RR, O’Neill JR. Summary of the American Heart Association scientific statement: Promoting physical activity in children and youth: A leadership role for schools. J Cardiovasc Nurs. 2008;23(1)
  3. Chaput JP, Willumsen J, Bull F, Chou R, Ekelund U, Firth J, et al. 2020 WHO guidelines on physical activity and sedentary behaviour for children and adolescents aged 5–17 years: summary of the evidence. Vol. 17, International Journal of Behavioral Nutrition and Physical Activity. 2020
  4. Pate RR, Davis MG, Robinson TN, Stone EJ, McKenzie TL, Young JC. Promoting physical activity in children and youth: A leadership role for schools - A scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism (Physical Activity Committee) in collaboration with the Councils on Cardiovascular Disease in the Young and Cardiovascular Nursing. Vol. 114, Circulation. 2006
  5. Steinberger J, Daniels SR, Hagberg N, Isasi CR, Kelly AS, Lloyd-Jones D, et al. Cardiovascular Health Promotion in Children: Challenges and Opportunities for 2020 and Beyond: A Scientific Statement from the American Heart Association. Circulation. 2016;134(12)
  6. Voltarelli VA, Fernandes LG, Brum PC. Cellular and molecular exercise physiology. Rev Bras Educ Física e Esporte. 2020;34(3)
  7. Powers S, Howley E. Exercise Physiology; Theory and Application to Fitness and Performance. New York, USA: McGraw-Hill Education; 2018
  8. Vega RB, Konhilas JP, Kelly DP, Leinwand LA. Molecular Mechanisms Underlying Cardiac Adaptation to Exercise. Vol. 25, Cell Metabolism. 2017
  9. Platt C, Houstis N, Rosenzweig A. Using exercise to measure and modify cardiac function. Vol. 21, Cell Metabolism. 2015
  10. Bernardo BC, Weeks KL, Pretorius L, McMullen JR. Molecular distinction between physiological and pathological cardiac hypertrophy: Experimental findings and therapeutic strategies. Vol. 128, Pharmacology and Therapeutics. 2010
  11. Dorn GW. The fuzzy logic of physiological cardiac hypertrophy. Vol. 49, Hypertension. 2007
  12. Oldfield CJ, Duhamel TA, Dhalla NS. Mechanisms for the transition from physiological to pathological cardiac hypertrophy. Vol. 98, Canadian Journal of Physiology and Pharmacology. 2020
  13. Kleber AG, Saffitz JE. Role of the intercalated disc in cardiac propagation and arrhythmogenesis. Vol. 5, Frontiers in Physiology. 2014
  14. Fountoulaki K, Dagres N. Cellular Communications in the Heart. Card Fail Rev [Internet]. 2015;1(2):64. Available from:
  15. Saffitz JE, Kléber AG. Effects of Mechanical Forces and Mediators of Hypertrophy on Remodeling of Gap Junctions in the Heart. Vol. 94, Circulation Research. 2004
  16. Jansen JA, van Veen TAB, de Bakker JMT, van Rijen HVM. Cardiac connexins and impulse propagation. Vol. 48, Journal of Molecular and Cellular Cardiology. 2010
  17. Desplantez T. Cardiac Cx43, Cx40 and Cx45 co-assembling: Involvement of connexins epitopes in formation of hemichannels and Gap junction channels. Vol. 18, BMC Cell Biology. 2017
  18. Michela P, Velia V, Aldo P, Ada P. Role of connexin 43 in cardiovascular diseases. Vol. 768, European Journal of Pharmacology. 2015
  19. George SA, Poelzing S. Cardiac conduction in isolated hearts of genetically modified mice - Connexin43 and salts. Prog Biophys Mol Biol. 2016;120(1–3)
  20. Fontes MSC, Van Veen TAB, De Bakker JMT, Van Rijen HVM. Functional consequences of abnormal Cx43 expression in the heart. Biochim Biophys Acta - Biomembr. 2012;1818(8)
  21. Kim E, Fishman GI. Designer gap junctions that prevent cardiac arrhythmias. Vol. 23, Trends in Cardiovascular Medicine. 2013
  22. Chondro F, Siagian M, Santoso DI. Aerobic exercise increases connexin43 expression in rat cardiac muscle. UNIVERSA Med. 2013;Vol.32-N(September-December):155–64
  23. Kadow Z, Jepson A, Firkins R, Davenport A, Henry M, Moffitt J. The effects of moderate intensity exercise training on the incidence of supraventricular arrhythmias and atrial connexin40 and connexin43 expression in young and aged rats (881.3). The. FASEB J. 2014;28(881):3
  24. Hsu YC, Chen HI, Kuo YM, Yu L, Huang TY, Chen SJ, et al. Chronic treadmill running in normotensive rats resets the resting blood pressure to lower levels by upregulating the hypothalamic GABAergic system. J Hypertens. 2011;29(12)
  25. Wagener A, Schmitt AO, Brockmann GA. Early and late onset of voluntary exercise have differential effects on the metabolic syndrome in an obese mouse model. Exp Clin Endocrinol Diabetes. 2012;120(10)
  26. Salameh A, Krautblatter S, Karl S, Blanke K, Gomez DR, Dhein S, et al. The signal transduction cascade regulating the expression of the gap junction protein connexin43 by β-adrenoceptors. Br J Pharmacol [Internet]. 2009 Sep;158(1):198–208. Available from:
  27. Salameh A, Dhein S. Effects of mechanical forces and stretch on intercellular gap junction coupling. Vol. 1828, Biochimica et Biophysica Acta - Biomembranes. 2013
  28. Bellafiore M, Sivverini G, Palumbo D, Macaluso F, Bianco A, Palma A, et al. Increased Cx43 and angiogenesis in exercised mouse hearts. Int J Sports Med. 2007;28(9)
  29. Jepson A., Garnett E., Davenport A., Firkins R., Kadow Z., Henry M., et al. The Effects of Exercise Training (ET) on Cardiac Arrhythmias and Left Ventricular (LV) Connexin 43 (Cx43) Expression in Aged and Young Rats. FASEB J. 2013;27:711.12-711.12
  30. Jin H, Chemaly ER, Lee A, Kho C, Hadri L, Hajjar RJ, et al. Mechanoelectrical remodeling and arrhythmias during progression of hypertrophy. FASEB J [Internet]. 2010 Feb 13;24(2):451–63. Available from:
  31. Benfato ID, Moretto TL, Barthichoto M, De Carvalho FP, De Oliveira CAM. Translational Science: How experimental research has contributed to the understanding of spontaneous Physical Activity and Energy Homeostasis. Vol. 23, Motriz. Revista de Educacao Fisica. 2017
  32. Greenwood BN, Loughridge AB, Sadaoui N, Christianson JP, Fleshner M. The protective effects of voluntary exercise against the behavioral consequences of uncontrollable stress persist despite an increase in anxiety following forced cessation of exercise. Behav Brain Res [Internet]. 2012 Aug;233(2):314–21. Available from:
  33. Tiscornia GC, Moretta R, Argenziano MA, Amorena CE, Garcia Gras EA. Inhibition of connexin 43 in cardiac muscle during intense physical exercise. Scand J Med Sci Sport. 2014;24(2)
  34. Basheer WA, Shaw RM. Connexin 43 and CaV1.2 Ion Channel Trafficking in Healthy and Diseased Myocardium. Circ Arrhythmia Electrophysiol [Internet]. 2016 Jun;9(6). Available from:
  35. Totland MZ, Rasmussen NL, Knudsen LM, Leithe E. Regulation of gap junction intercellular communication by connexin ubiquitination: physiological and pathophysiological implications. Vol. 77, Cellular and Molecular Life Sciences. 2020
  36. Kostin S, Dammer S, Hein S, Klovekorn WP, Bauer EP, Schaper J. Connexin 43 expression and distribution in compensated and decompensated cardiac hypertrophy in patients with aortic stenosis. Cardiovasc Res. 2004;62(2)
  37. Bouvard C, Genet N, Phan C, Rode B, Thuillet R, Tu L, et al. Connexin-43 is a promising target for pulmonary hypertension due to hypoxaemic lung disease. Eur Respir J. 2020;55(3)
  38. Severs NJ, Bruce AF, Dupont E, Rothery S. Remodelling of gap junctions and connexin expression in diseased myocardium. Vol. 80, Cardiovascular Research. 2008
  39. Seidel T, Salameh A, Dhein S. A simulation study of cellular hypertrophy and connexin lateralization in cardiac tissue. Biophys J. 2010;99(9)

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