Effect of High Interval Intensity Training and Aerobic Exercise on the Content of the SERCA2a and Phospholamban Proteins in Slow-Twitch and Fast Twitch Muscles of Wistar Rat

Document Type : Original Article


1 PHD Student of Exercise Physiology.Department of Exercise Physiology, Faculty of Sport Science, Esfahan University, Esfahan, Iran.

2 Professor of Exercise Physiology.Department of Exercise Physiology, Faculty of Sport Science, Esfahan University, Esfahan, Iran.


Background and Objective: The control of cytosolic calcium is precisely due to its major role in the muscle contraction. So, we investigated the changes in FULL NAME FIRST (SERCA2a), the most important calcium transmitter, and its inhibitory, (Phospholamban Proteins (PLN), with exercise.
Subjects and Methods: Eighteen adult male Wistar rats were placed in three groups, aerobic exercise training (AET), high intensity interval training (HIIT), and control group (CO) .The AET and HIIT groups ran on treadmill at speeds of 12-15 (m/min), and 25 to 30 (m/min), respectively, 5 days a week for 8 weeks. At the end, the extensor digitorum longus (EDL) and soleus (sol) muscles were extracted and the concentration of SERCA2a and PLN proteins were measured using ELISA kits. One way ANOVA, independent t-test, and two-way analyze of variance at the significance level (α = 0.05) were used.
Results: In terms of SERCA2a, there was a significant difference between the EDL and SOL muscles in the control group (P=0.001) and the AET group (P=0.030). Also, there was a significant difference in PLN between EDL and SOL muscles only in the AET group (P=0.007). Also, there was a significant difference between the control groups, AET and HIIT in terms of SERCA2a (P=0.046) and PLN (P=0.006). In addition, an interactive effect was observed between exercise intensity and muscle fiber type on the SERCA2a (P =0.042) and also PLN (P = 0.008).
Conclusion: To achieve optimal muscle function, especially factors affecting calcium transmission, it is necessary to consider simultaneously the type of muscle fiber and the intensity of exercise appropriate to it.


1-Bers DM. Cardiac excitation–contraction coupling. Nature. 2002;415(6868):198-205.
2-Shaikh SA. Regulation of the Sarco-endoplasmic Reticulum Calcium ATPase by Sarcolipin: The Ohio State University; 2015.
3-Martin PD, James ZM, Thomas DD. Effect of Phosphorylation on Interactions between Transmembrane Domains of SERCA and Phospholamban. Biophysical journal. 2018;114(11):2573-83.
4-Durkin SS, Ward MD, Fryrear KA, Semmes OJ. Site-specific phosphorylation differentiates active from inactive forms of the human T-cell leukemia virus type 1 Tax oncoprotein. Journal of Biological Chemistry. 2006;281(42):31705-12.
5-Berchtold MW, Brinkmeier H, Müntener M. Calcium ion in skeletal muscle: its crucial role for muscle function, plasticity, and disease. Physiological reviews. 2000;80(3):1215-65.
6-Fabiato A. Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. American Journal of Physiology-Cell Physiology. 1983;245(1):C1-C14.
7-Bers DM. Ca transport during contraction and relaxation in mammalian ventricular muscle. Basic research in cardiology. 1997;92(s 1):1-10.
8-MacLennan DH, Kranias EG. Phospholamban: a crucial regulator of cardiac contractility. Nature reviews Molecular cell biology. 2003;4(7):566.
9-Mustroph J, Wagemann O, Lebek S, Tarnowski D, Ackermann J, Drzymalski M, et al. SR Ca2+-leak and disordered excitation-contraction coupling as the basis for arrhythmogenic and negative inotropic effects of acute ethanol exposure. Journal of molecular and cellular cardiology. 2018;116:81-90.
10-Wuytack F, Raeymaekers L, Missiaen L. Molecular physiology of the SERCA and SPCA pumps. Cell calcium. 2002;32(5):279-305.
11-Hovnanian A. SERCA pumps and human diseases.  Calcium Signalling and disease: Springer; 2007. p. 337-63.
12-Periasamy M, Kalyanasundaram A. SERCA pump isoforms: their role in calcium transport and disease. Muscle & nerve. 2007;35(4):430-42.
13-Treves S, Jungbluth H, Voermans N, Muntoni F, Zorzato F, editors. Ca2+ handling abnormalities in early-onset muscle diseases: Novel concepts and perspectives. Seminars in cell & developmental biology; 2017: Elsevier.
14-Nie L, Yuan X-L, Jiang K-T, Jiang Y-H, Yuan J, Luo L, et al. Salsalate Activates Skeletal Muscle Thermogenesis and Protects Mice from High-Fat Diet Induced Metabolic Dysfunction. EBioMedicine. 2017;23:136-45.
15-Razvi S, Jabbar A, Pingitore A, Danzi S, Biondi B, Klein I, et al. Thyroid Hormones and Cardiovascular Function and Diseases. Journal of the American College of Cardiology. 2018;71(16):1781-96.
16-Silva GJ, Bye A, el Azzouzi H, Wisløff U. MicroRNAs as important regulators of exercise adaptation. Progress in cardiovascular diseases. 2017;60(1):130-51.
17-Stammers AN, Susser SE, Hamm NC, Hlynsky MW, Kimber DE, Kehler DS, et al. The regulation of sarco (endo) plasmic reticulum calcium-ATPases (SERCA). Canadian journal of physiology and pharmacology. 2015;93(10):843-54.
18-Periasamy M, Bhupathy P, Babu GJ. Regulation of sarcoplasmic reticulum Ca2+ ATPase pump expression and its relevance to cardiac muscle physiology and pathology. Cardiovascular research. 2007;77(2):265-73.
19-Kemi OJ, Ellingsen Ø, Ceci M, Grimaldi S, Smith GL, Condorelli G, et al. Aerobic interval training enhances cardiomyocyte contractility and Ca 2+ cycling by phosphorylation of CaMKII and Thr-17 of phospholamban. Journal of molecular and cellular cardiology. 2007;43(3):354-61.
20-Duhamel T, Stewart R, Tupling AR, Ouyang J, Green H. Muscle sarcoplasmic reticulum calcium regulation in humans during consecutive days of exercise and recovery. Journal of Applied Physiology. 2007;103(4):1212-20.
21-Ferreira JC, Bacurau AV, Bueno CR, Cunha TC, Tanaka LY, Jardim MA, et al. Aerobic exercise training improves Ca2+ handling and redox status of skeletal muscle in mice. Experimental Biology and Medicine. 2010;235(4):497-505.
22-Farrell PA, Joyner MJ, Caiozzo VJ, Medicine ACoS. ACSM’s advanced exercise physiology. American Colledge of Sports Medicine. 2012:241-44.
23-Wisløff U, Loennechen JP, Currie S, Smith GL, Ellingsen Ø. Aerobic exercise reduces cardiomyocyte hypertrophy and increases contractility, Ca2+ sensitivity and SERCA-2 in rat after myocardial infarction. Cardiovascular research. 2002;54(1):162-74.
24-Bupha-Intr T, Laosiripisan J, Wattanapermpool J. Moderate intensity of regular exercise improves cardiac SR Ca 2+ uptake activity in ovariectomized rats. Journal of Applied Physiology. 2009;107(4):1105-12.
25-Johnsen AB, Høydal M, Røsbjørgen R, Stølen T, Wisløff U. Aerobic interval training partly reverse contractile dysfunction and impaired Ca2+ handling in atrial myocytes from rats with post infarction heart failure. PloS one. 2013;8(6):e66288.
26-Morissette MP, Susser SE, Stammers AN, O'Hara KA, Gardiner PF, Sheppard P, et al. Differential regulation of the fiber type-specific gene expression of the sarcoplasmic reticulum calcium-ATPase isoforms induced by exercise training. Journal of Applied Physiology. 2014;117(5):544-55.
27-MacDonnell SM, Kubo H, Crabbe DL, Renna BF, Reger PO, Mohara J, et al. Improved myocardial β-adrenergic responsiveness and signaling with exercise training in hypertension. Circulation. 2005;111(25):3420-8.
28-Pacagnelli FL, Sabela A, Dias AK, Okoshi K, Mariano TB, Campos DHS, et al. Preventive aerobic training exerts a cardioprotective effect on rats treated with monocrotaline. International journal of experimental pathology. 2016;97(3):238-47.
29-Moreira-Gonçalves D, Ferreira R, Fonseca H, Padrão AI, Moreno N, Silva AF, et al. Cardioprotective effects of early and late aerobic exercise training in experimental pulmonary arterial hypertension. Basic research in cardiology. 2015;110(6):57.
30-Soares L, Drummond F, Lavorato V, Carneiro-Junior M, Natali A. Exercise training and pulmonary arterial hypertension: A review of the cardiac benefits. Science & Sports. 2018.
31-Rose AJ, Frøsig C, Kiens B, Wojtaszewski JF, Richter EA. Effect of endurance exercise training on Ca2+–calmodulin‐dependent protein kinase II expression and signalling in skeletal muscle of humans. The Journal of physiology. 2007;583(2):785-95.
32-Høydal MA, Wisløff U, Kemi OJ, Ellingsen Ø. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. European Journal of Cardiovascular Prevention & Rehabilitation. 2007;14(6):753-60.
33-Eng CM, Smallwood LH, Rainiero MP, Lahey M, Ward SR, Lieber RL. Scaling of muscle architecture and fiber types in the rat hindlimb. Journal of Experimental Biology. 2008;211(14):2336-45.
34-Bueno CR, Ferreira JCB, Pereira MG, Bacurau AV, Brum PC. Aerobic exercise training improves skeletal muscle function and Ca 2+ handling-related protein expression in sympathetic hyperactivity-induced heart failure. Journal of Applied Physiology. 2010;109(3):702-9.
35-Tupling AR, Bombardier E, Gupta SC, Hussain D, Vigna C, Bloemberg D, et al. Enhanced Ca 2+ transport and muscle relaxation in skeletal muscle from sarcolipin-null mice. American Journal of Physiology-Cell Physiology. 2011;301(4):C841-C9.
36-Sahlin K, Tonkonogi M, Söderlund K. Energy supply and muscle fatigue in humans. Acta physiologica. 1998;162(3):261-6.
37-Smith IC, Bombardier E, Vigna C, Tupling AR. ATP consumption by sarcoplasmic reticulum Ca2+ pumps accounts for 40-50% of resting metabolic rate in mouse fast and slow twitch skeletal muscle. PloS one2013;8(7) e68924.
38-Bidasee KR, Zhang Y, Shao CH, Wang M, Patel KP, Dincer ÜD, et al. Diabetes increases formation of advanced glycation end products on Sarco (endo) plasmic reticulum Ca2+-ATPase. Diabetes. 2004;53(2):463-73.
39-Clark RJ, McDonough PM, Swanson E, Trost SU, Suzuki M, Fukuda M, et al. Diabetes and the accompanying hyperglycemia impairs cardiomyocyte calcium cycling through increased nuclear O-GlcNAcylation. Journal of Biological Chemistry. 2003;278(45):44230-7.
40-Hu Y, Belke D, Suarez J, Swanson E, Clark R, Hoshijima M, et al. Adenovirus-mediated overexpression of O-GlcNAcase improves contractile function in the diabetic heart. Circulation research. 2005;96(9):1006-13.
41-Kho C, Lee A, Jeong D, Oh JG, Chaanine AH, Kizana E, et al. SUMO1-dependent modulation of SERCA2a in heart failure. Nature. 2011;477(7366):601.
42-Norrbom J, Wallman S, Gustafsson T, Rundqvist H, Jansson E, Sundberg C. Training response of mitochondrial transcription factors in human skeletal muscle. Acta physiologica. 2010;198(1):71-9.
43-Shirwany NA, Zou M-H. AMPK in cardiovascular health and disease. Acta pharmacologica Sinica. 2010;31(9):1075.
44-Mu J, Brozinick Jr JT, Valladares O, Bucan M, Birnbaum MJ. A role for AMP-activated protein kinase in contraction-and hypoxia-regulated glucose transport in skeletal muscle. Molecular cell. 2001;7(5):1085-94.
45-Lee-Young RS, Canny BJ, Myers DE, McConell GK. AMPK activation is fiber type specific in human skeletal muscle: effects of exercise and short-term exercise training. Journal of Applied Physiology. 2009;107(1):283-9.
46-Vanderburg CR, Clarke MS. Laser capture microdissection of metachromatically stained skeletal muscle allows quantification of fiber type specific gene expression. Molecular and cellular biochemistry. 2013;375(1-2):159-70.
47-Guo J, Bian Y, Bai R, Li H, Fu M, Xiao C. Globular adiponectin attenuates myocardial ischemia/reperfusion injury by upregulating endoplasmic reticulum Ca2+-ATPase activity and inhibiting endoplasmic reticulum stress. Journal of cardiovascular pharmacology. 2013;62(2):143-53.
48-Anderson DM, Anderson KM, Chang C-L, Makarewich CA, Nelson BR, McAnally JR, et al. A micropeptide encoded by a putative long noncoding RNA regulates muscle performance. Cell. 2015;160(4):595-606.