Decreased intracellular [Ca2+] coincides with reduced expression of Dhprα1s, RyR1, and diaphragmatic dysfunction in a rat model of sepsis
Meng-meng Wang MD
Department of Respiratory and Intensive Care Unit, Shengjing Hospital of China Medical University, Shenyang, Postal Code 110004 People's Republic of China
Search for more papers by this authorLi-ying Hao PhD
Department of Pharmaceutical Toxicology, School of Pharmaceutical Sciences, China Medical University, Shenyang, People's Republic of China
Search for more papers by this authorFeng Guo MD
Department of Pharmaceutical Toxicology, School of Pharmaceutical Sciences, China Medical University, Shenyang, People's Republic of China
Search for more papers by this authorBin Zhong MD
Department of Respiratory Medicine, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi Province, People's Republic of China
Search for more papers by this authorXiao-mei Zhong MD
Department of Respiratory and Intensive Care Unit, Shengjing Hospital of China Medical University, Shenyang, Postal Code 110004 People's Republic of China
Search for more papers by this authorJing Yuan MD
Department of Respiratory and Intensive Care Unit, Shengjing Hospital of China Medical University, Shenyang, Postal Code 110004 People's Republic of China
Search for more papers by this authorYi-fei Hao MD
Department of Orthopedic Surgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China
Search for more papers by this authorShuang Zhao MD
Department of Respiratory and Intensive Care Unit, Shengjing Hospital of China Medical University, Shenyang, Postal Code 110004 People's Republic of China
Search for more papers by this authorXue-fei Sun MD
Department of Pharmaceutical Toxicology, School of Pharmaceutical Sciences, China Medical University, Shenyang, People's Republic of China
Search for more papers by this authorMing Lei MD
Department of Pharmaceutical Toxicology, School of Pharmaceutical Sciences, China Medical University, Shenyang, People's Republic of China
Search for more papers by this authorCorresponding Author
Guang-yu Jiao MD, PhD
Department of Respiratory and Intensive Care Unit, Shengjing Hospital of China Medical University, Shenyang, Postal Code 110004 People's Republic of China
Correspondence to: G.-Y. Jiao; e-mail: [email protected]Search for more papers by this authorMeng-meng Wang MD
Department of Respiratory and Intensive Care Unit, Shengjing Hospital of China Medical University, Shenyang, Postal Code 110004 People's Republic of China
Search for more papers by this authorLi-ying Hao PhD
Department of Pharmaceutical Toxicology, School of Pharmaceutical Sciences, China Medical University, Shenyang, People's Republic of China
Search for more papers by this authorFeng Guo MD
Department of Pharmaceutical Toxicology, School of Pharmaceutical Sciences, China Medical University, Shenyang, People's Republic of China
Search for more papers by this authorBin Zhong MD
Department of Respiratory Medicine, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi Province, People's Republic of China
Search for more papers by this authorXiao-mei Zhong MD
Department of Respiratory and Intensive Care Unit, Shengjing Hospital of China Medical University, Shenyang, Postal Code 110004 People's Republic of China
Search for more papers by this authorJing Yuan MD
Department of Respiratory and Intensive Care Unit, Shengjing Hospital of China Medical University, Shenyang, Postal Code 110004 People's Republic of China
Search for more papers by this authorYi-fei Hao MD
Department of Orthopedic Surgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China
Search for more papers by this authorShuang Zhao MD
Department of Respiratory and Intensive Care Unit, Shengjing Hospital of China Medical University, Shenyang, Postal Code 110004 People's Republic of China
Search for more papers by this authorXue-fei Sun MD
Department of Pharmaceutical Toxicology, School of Pharmaceutical Sciences, China Medical University, Shenyang, People's Republic of China
Search for more papers by this authorMing Lei MD
Department of Pharmaceutical Toxicology, School of Pharmaceutical Sciences, China Medical University, Shenyang, People's Republic of China
Search for more papers by this authorCorresponding Author
Guang-yu Jiao MD, PhD
Department of Respiratory and Intensive Care Unit, Shengjing Hospital of China Medical University, Shenyang, Postal Code 110004 People's Republic of China
Correspondence to: G.-Y. Jiao; e-mail: [email protected]Search for more papers by this authorThis project was supported by the National Natural Science Foundation of China (81170068 to G.-Y. Jiao, 81100108 to L.-Y.H., 81471323 to F.G.) and the Natural Science Foundation of Liaoning Province (2015020521 to G.-Y.J.).
ABSTRACT
Introduction
Sepsis can cause decreased diaphragmatic contractility. Intracellular calcium as a second messenger is central to diaphragmatic contractility. However, changes in intracellular calcium concentration ([Ca2+]) and the distribution and co-localization of relevant calcium channels [dihydropyridine receptors, (DHPRα1s) and ryanodine receptors (RyR1)] remain unclear during sepsis. In this study we investigated the effect of changed intracellular [Ca2+] and expression and distribution of DHPRα1s and RyR1 on diaphragm function during sepsis.
Methods
We measured diaphragm contractility and isolated diaphragm muscle cells in a rat model of sepsis. The distribution and co-localization of DHPRα1s and RyR1 were determined using immunohistochemistry and immunofluorescence, whereas intracellular [Ca2+] was measured by confocal microscopy and fluorescence spectrophotometry.
Results
Septic rat diaphragm contractility, expression of DHPRα1s and RyR1, and intracellular [Ca2+] were significantly decreased in the rat sepsis model compared with controls.
Discussion
Decreased intracellular [Ca2+] coincides with diaphragmatic contractility and decreased expression of DHPRα1s and RyR1 in sepsis. Muscle Nerve 56: 1128–1136, 2017
REFERENCES
- 1 Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Committee ASCC. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. 1992. Chest 2009; 136(suppl): e28.
- 2 Nguyen HB, Van Ginkel C, Batech M, Banta J, Corbett SW. Comparison of Predisposition, Insult/Infection, Response, and Organ Dysfunction, Acute Physiology and Chronic Health Evaluation II, and Mortality in Emergency Department Sepsis in patients meeting criteria for early goal-directed therapy and the severe sepsis resuscitation bundle. J Crit Care 2012; 27: 362–369.
- 3 Wu J, Zhang J, Gong Y, Li S. Slowed relaxation of diaphragm in septic rats is associated with reduced expression of sarco-endoplasmic reticulum Ca-ATPase genes SERCA1 and SERCA 2. Muscle Nerve 2016; 54: 1108–1113.
- 4 Sadowitz B, Roy S, Gatto LA, Habashi N, Nieman G. Lung injury induced by sepsis: lessons learned from large animal models and future directions for treatment. Expert Rev Anti-infective Ther 2011; 9: 1169–1178.
- 5 Sevransky JE, Martin GS, Mendez-Tellez P, Shanholtz C, Brower R, Pronovost PJ, et al. Pulmonary vs nonpulmonary sepsis and mortality in acute lung injury. Chest 2008; 134: 534–538.
- 6 Sevransky JE, Martin GS, Shanholtz C, Mendez-Tellez PA, Pronovost P, Brower R, et al. Mortality in sepsis versus non-sepsis induced acute lung injury. Crit Care 2009; 13: R150.
- 7 Supinski G, Nethery D, Stofan D, DiMarco A. Comparison of the effects of endotoxin on limb, respiratory, and cardiac muscles. J Appl Physiol 1996; 81: 1370–1378.
- 8 Supinski GS, Wang W, Callahan LA. Caspase and calpain activation both contribute to sepsis-induced diaphragmatic weakness. J Appl Physiol 2009; 107: 1389–1396.
- 9 Jiao GY, Hao LY, Gao CE, Chen L, Sun XF, Yang HL, et al. Reduced DHPRalpha1S and RyR1 expression levels are associated with diaphragm contractile dysfunction during sepsis. Muscle Nerve 2013; 48: 745–751.
- 10 Shindoh C, Murakami Y, Shishido R, Sasaki K, Nishio T, Miura M. Tulobuterol patch maintains diaphragm muscle contractility for over twenty-four hours in a mouse model of sepsis. Tohoku J Exp Med 2009; 218: 271–278.
- 11 Wilson TA, Legrand A, Gevenois PA, De Troyer A. Respiratory effects of the external and internal intercostal muscles in humans. J Physiol 2001; 530: 319–330.
- 12 Supinski GS, Callahan LA. Hemin prevents cardiac and diaphragm mitochondrial dysfunction in sepsis. Free Rad Biol Med 2006; 40: 127–137.
- 13 Callahan LA, Supinski GS. Downregulation of diaphragm electron transport chain and glycolytic enzyme gene expression in sepsis. J Appl Physiol 2005; 99: 1120–1126.
- 14 Lacomis D, Giuliani MJ, van Cott A, Kramer DJ. Acute myopathy of intensive care: clinical, electromyographic, and pathological aspects. Ann Neurol 1996; 40: 645–654.
- 15 Lanone S, Taille C, Boczkowski J, Aubier M. Diaphragmatic fatigue during sepsis and septic shock. Intensive Care Med 2005; 31: 1611–1617.
- 16 Boczkowski J, Lanone S, Ungureanu-Longrois D, Danialou G, Fournier T, Aubier M. Induction of diaphragmatic nitric oxide synthase after endotoxin administration in rats: role on diaphragmatic contractile dysfunction. J Clin Invest 1996; 98: 1550–1559.
- 17 Rebbeck RT, Karunasekara Y, Board PG, Beard NA, Casarotto MG, Dulhunty AF. Skeletal muscle excitation-contraction coupling: who are the dancing partners? Int J Biochem Cell Biol 2014; 48: 28–38.
- 18 Luo Y, Rall JA. Regulation of contraction kinetics in skinned skeletal muscle fibers by calcium and troponin C. Arch Bioch Biophys 2006; 456: 119–126.
- 19 Clancy JS, Takeshima H, Hamilton SL, Reid MB. Contractile function is unaltered in diaphragm from mice lacking calcium release channel isoform 3. Am J Physiol 1999; 277: R1205–1209.
- 20 Fill M, Copello JA. Ryanodine receptor calcium release channels. Physiol Rev 2002; 82: 893–922.
- 21 Ogawa Y, Kurebayashi N, Murayama T. Putative roles of type 3 ryanodine receptor isoforms (RyR3). Trends Cardiovasc Med 2000; 10: 65–70.
- 22 Andersson DC, Marks AR. Fixing ryanodine receptor Ca leak—a novel therapeutic strategy for contractile failure in heart and skeletal muscle. Drug Discov Today Dis Mech 2010; 7: e151–e157.
- 23 Yang M, Wang H, Han G, Chen L, Huang L, Jiang J, et al. Phrenic nerve stimulation protects against mechanical ventilation-induced diaphragm dysfunction in rats. Muscle Nerve 2013; 48: 958–962.
- 24 Jiao GY, Hao LY, Chen L, Gao CE, Feng R, Hu HY, et al. High levels of positive end-expiratory pressure preserve diaphragmatic contractility during acute respiratory distress syndrome in rats. Exp Physiol 2015; 100: 967–976.
- 25 Sassoon CS, Zhu E, Fang L, Ramar K, Jiao GY, Caiozzo VJ. Interactive effects of corticosteroid and mechanical ventilation on diaphragm muscle function. Muscle Nerve 2011; 43: 103-111.
- 26 Gu J, Liang Y, Qiao L, Li X, Li X, Lu Y, et al. Expression analysis of URI/RMP gene in endometrioid adenocarcinoma by tissue microarray immunohistochemistry. Int J Clin Exp Pathol 2013; 6: 2396–2403.
- 27 Huang X, Li D, Li T, Zhao BO, Chen X. Prognostic value of the expression of phosphatase and tensin homolog and CD44 in elderly patients with refractory acute myeloid leukemia. Oncol Lett 2015; 10: 103–110.
- 28 Toussaint A, Cowling BS, Hnia K, Mohr M, Oldfors A, Schwab Y, et al. Defects in amphiphysin 2 (BIN1) and triads in several forms of centronuclear myopathies. Acta Neuropathol 2011; 121: 253–266.
- 29 Guo F, Zhou PD, Gao QH, Gong J, Feng R, Xu XX, et al. Low-Mg(2+) treatment increases sensitivity of voltage-gated Na(+) channels to Ca(2+)/calmodulin-mediated modulation in cultured hippocampal neurons. Am J Physiol Cell Physiol 2015; 308: C594–605.
- 30 Schwerzmann K, Cruz-Orive LM, Eggman R, Sanger A, Weibel ER. Molecular architecture of the inner membrane of mitochondria from rat liver: a combined biochemical and stereological study. J Cell Biol 1986; 102: 97–103.
- 31 Mathieu O, Cruz-Orive LM, Hoppeler H, Weibel ER. Measuring error and sampling variation in stereology: comparison of the efficiency of various methods for planar image analysis. J Microsc 1981; 121: 75–88.
- 32 Pinheiro DF, da Silva RF, Carvalho LP, Paiva-Oliveira EL, Pereira RS, Leite PE, et al. Persistent activation of omentum influences the pattern of muscular lesion in the mdx diaphragm. Cell Tissue Res 2012; 350: 77–88.
- 33 Danoviz ME, Yablonka-Reuveni Z. Skeletal muscle satellite cells: background and methods for isolation and analysis in a primary culture system. Methods Mol Biol 2012; 798: 21–52.
- 34 Kim JH, Lee JO, Lee SK, Jung JH, You GY, Park SH, et al. Clozapine activates AMP-activated protein kinase (AMPK) in C2C12 myotube cells and stimulates glucose uptake. Life Sci 2010; 87: 42–48.
- 35 Yan H, Chen X, Li J, Feng Y, Shi Z, Wang X, et al. Synthesis of alginate derivative via the Ugi reaction and its characterization. Carbohydr Polym 2016; 136: 757–763.
- 36 Liu FC, Day YJ, Liou JT, Yu HP, Liao HR. Splitomicin inhibits fMLP-induced superoxide anion production in human neutrophils by activate cAMP/PKA signaling inhibition of ERK pathway. Eur J Pharmacol 2012; 688: 68–75.
- 37 Ito T, Fujimura N, Omote K, Namiki A. A selective beta2-adrenergic agonist, terbutaline, improves sepsis-induced diaphragmatic dysfunction in the rat. Life Sci 2006; 79: 905–912.
- 38 Supinski G, Nethery D, Nosek TM, Callahan LA, Stofan D, DiMarco A. Endotoxin administration alters the force vs. pCa relationship of skeletal muscle fibers. Am J Physiol Regul Integr Comparative Physiol 2000; 278: R891–896.
- 39 Sun J, Xu L, Eu JP, Stamler JS, Meissner G. Classes of thiols that influence the activity of the skeletal muscle calcium release channel. J Biol Chem 2001; 276: 15625–15630.
- 40 Liu SH, Lai JL, Yang RS, Lin-Shiau SY. Nitric oxide is not involved in the endotoxemia-induced alterations in Ca2 + and ryanodine responses in mouse diaphragms. Naunyn-Schmiedeberg Arch Pharmacol 2002; 366: 327–334.
- 41 MacFarlane NG, Darnley GM, Smith GL. Cellular basis for contractile dysfunction in the diaphragm from a rabbit infarct model of heart failure. Am J Physiol Cell Physiol 2000; 278: C739–746.
- 42 Ottenheijm CA, Heunks LM, Sieck GC, Zhan WZ, Jansen SM, Degens H, et al. Diaphragm dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005; 172: 200–205.
- 43 Lang B, Newsom-Davis J, Peers C, Prior C, Wray DW. The effect of myasthenic syndrome antibody on presynaptic calcium channels in the mouse. J Physiol 1987; 390: 257–270.
Citing Literature
