Calcium signaling in endocardial and epicardial ventricular myocytes from streptozotocin-induced diabetic rats
Corresponding Author
Lina T Al Kury
Department of Health Sciences, College of Natural and Health Sciences, Zayed University, Abu Dhabi, United Arab Emirates
Correspondence
Lina T Al Kury
Tel.: +971-50-662-3975
Fax: +971-2-443-4847
E-mail address: [email protected]
Search for more papers by this authorVadym Sydorenko
Department of Cellular Membranology, Bogomoletz Institute of Physiology, Kiev, Ukraine
Search for more papers by this authorManal MA Smail
Department of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
Search for more papers by this authorMuhammad A Qureshi
Department of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
Search for more papers by this authorAnatoly Shmygol
Department of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
Search for more papers by this authorDimitrios Papandreou
Department of Health Sciences, College of Natural and Health Sciences, Zayed University, Abu Dhabi, United Arab Emirates
Search for more papers by this authorJaipaul Singh
School of Forensic and Applied Sciences, University of Central Lancashire, Preston, UK
Search for more papers by this authorFrank Christopher Howarth
Department of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
Search for more papers by this authorCorresponding Author
Lina T Al Kury
Department of Health Sciences, College of Natural and Health Sciences, Zayed University, Abu Dhabi, United Arab Emirates
Correspondence
Lina T Al Kury
Tel.: +971-50-662-3975
Fax: +971-2-443-4847
E-mail address: [email protected]
Search for more papers by this authorVadym Sydorenko
Department of Cellular Membranology, Bogomoletz Institute of Physiology, Kiev, Ukraine
Search for more papers by this authorManal MA Smail
Department of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
Search for more papers by this authorMuhammad A Qureshi
Department of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
Search for more papers by this authorAnatoly Shmygol
Department of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
Search for more papers by this authorDimitrios Papandreou
Department of Health Sciences, College of Natural and Health Sciences, Zayed University, Abu Dhabi, United Arab Emirates
Search for more papers by this authorJaipaul Singh
School of Forensic and Applied Sciences, University of Central Lancashire, Preston, UK
Search for more papers by this authorFrank Christopher Howarth
Department of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
Search for more papers by this authorAbstract
Aims/Introduction
Abnormalities in Ca2+ signaling have a key role in hemodynamic dysfunction in diabetic heart. The purpose of this study was to explore the effects of streptozotocin (STZ)-induced diabetes on Ca2+ signaling in epicardial (EPI) and endocardial (ENDO) cells of the left ventricle after 5–6 months of STZ injection.
Materials and Methods
Whole-cell patch clamp was used to measure the L-type Ca2+ channel (LTCC) and Na+/Ca2+ exchanger currents. Fluorescence photometry techniques were used to measure intracellular free Ca2+ concentration.
Results
Although the LTCC current was not significantly altered, the amplitude of Ca2+ transients increased significantly in EPI-STZ and ENDO-STZ compared with controls. Time to peak LTCC current, time to peak Ca2+ transient, time to half decay of LTCC current and time to half decay of Ca2+ transients were not significantly changed in EPI-STZ and ENDO-STZ myocytes compared with controls. The Na+/Ca2+ exchanger current was significantly smaller in EPI-STZ and in ENDO-STZ compared with controls.
Conclusions
STZ-induced diabetes resulted in an increase in amplitude of Ca2+ transients in EPI and ENDO myocytes that was independent of the LTCC current. Such an effect can be attributed, at least in part, to the dysfunction of the Na+/Ca2+ exchanger. Additional studies are warranted to improve our understanding of the regional impact of diabetes on Ca2+ signaling, which will facilitate the discovery of new targeted treatments for diabetic cardiomyopathy.
Disclosure
The authors declare no conflict of interest.
Supporting Information
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| jdi13451-sup-0001-SupInfo.docxWord document, 15.7 KB | Appendix S1 | Solutions and reagents. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1Eisner DA, Caldwell JL, Kistamas K, et al. Calcium and excitation-contraction coupling in the heart. Circ Res 2017; 121: 181–195.
- 2Bodi I, Mikala G, Koch SE, et al. The L-type calcium channel in the heart: the beat goes on. J Clin Investig 2005; 115: 3306–3317.
- 3Walsh C, Barrow S, Voronina S, et al. Modulation of calcium signalling by mitochondria. Biochim Biophys Acta 2009; 1787: 1374–1382.
- 4Shao CH, Rozanski GJ, Patel KP, et al. Dyssynchronous (non-uniform) Ca2+ release in myocytes from streptozotocin-induced diabetic rats. J Mol Cell Cardiol 2007; 42: 234–246.
- 5Howarth FC, Almugaddum FA, Qureshi MA, et al. The effects of heavy long-term exercise on ventricular myocyte shortening and intracellular Ca2+ in streptozotocin-induced diabetic rat. J Diabetes Complications 2010; 24: 278–285.
- 6Ren J, Walsh MF, Hamaty M, et al. Altered inotropic response to IGF-I in diabetic rat heart: influence of intracellular Ca2+ and NO. Am J Physiol 1998; 275: H823–H830.
- 7Hattori Y, Matsuda N, Kimura J, et al. Diminished function and expression of the cardiac Na+-Ca2+ exchanger in diabetic rats: implication in Ca2+ overload. J Physiol 2000; 527(Pt 1): 85–94.
- 8Lee TI, Chen YC, Kao YH, et al. Rosiglitazone induces arrhythmogenesis in diabetic hypertensive rats with calcium handling alteration. Int J Cardiol 2013; 165: 299–307.
- 9Lagadic-Gossmann D, Buckler KJ, Le Prigent K, et al. Altered Ca2+ handling in ventricular myocytes isolated from diabetic rats. Am J Physiol 1996; 270(5 Pt 2): H1529–H1537.
- 10Takeda N, Dixon IM, Hata T, et al. Sequence of alterations in subcellular organelles during the development of heart dysfunction in diabetes. Diabetes Res Clin Pract 1996; 30(Suppl): 113–122.
- 11Choi KM, Zhong Y, Hoit BD, et al. Defective intracellular Ca(2+) signaling contributes to cardiomyopathy in Type 1 diabetic rats. Am J Physiol Heart Circ Physiol 2002; 283: H1398–H1408.
- 12Hamouda NN, Sydorenko V, Qureshi MA, et al. Dapagliflozin reduces the amplitude of shortening and Ca(2+) transient in ventricular myocytes from streptozotocin-induced diabetic rats. Mol Cell Biochem 2015; 400: 57–68.
- 13Chattou S, Diacono J, Feuvray D. Decrease in sodium-calcium exchange and calcium currents in diabetic rat ventricular myocytes. Acta Physiol Scand 1999; 166: 137–144.
- 14Shao CH, Wehrens XH, Wyatt TA, et al. Exercise training during diabetes attenuates cardiac ryanodine receptor dysregulation. J Appl Physiol 1985; 2009: 1280–1292.
- 15Tian C, Shao CH, Moore CJ, et al. Gain of function of cardiac ryanodine receptor in a rat model of type 1 diabetes. Cardiovasc Res 2011; 91: 300–309.
- 16Rithalia A, Qureshi MA, Howarth FC, et al. Effects of halothane on contraction and intracellular calcium in ventricular myocytes from streptozotocin-induced diabetic rats. Br J Anaesth 2004; 92: 246–253.
- 17Howarth FC, Qureshi MA. Effects of carbenoxolone on heart rhythm, contractility and intracellular calcium in streptozotocin-induced diabetic rat. Mol Cell Biochem 2006; 289: 21–29.
- 18Remme CA, Verkerk AO, Hoogaars WM, et al. The cardiac sodium channel displays differential distribution in the conduction system and transmural heterogeneity in the murine ventricular myocardium. Basic Res Cardiol 2009; 104: 511–522.
- 19Abd Allah ES, Aslanidi OV, Tellez JO, et al. Postnatal development of transmural gradients in expression of ion channels and Ca2⁺-handling proteins in the ventricle. J Mol Cell Cardiol 2012; 53: 145–155.
- 20Wang W, Gao J, Entcheva E, et al. A transmural gradient in the cardiac Na/K pump generates a transmural gradient in Na/Ca exchange. J Membr Biol 2010; 233: 51–62.
- 21Aït Mou Y, Reboul C, Andre L, et al. Late exercise training improves non-uniformity of transmural myocardial function in rats with ischaemic heart failure. Cardiovasc Res 2009; 81: 555–564.
- 22Lu Z, Jiang YP, Xu XH, et al. Decreased L-type Ca2+ current in cardiac myocytes of type 1 diabetic Akita mice due to reduced phosphatidylinositol 3-kinase signaling. Diabetes 2007; 56: 2780–2789.
- 23Teshima Y, Takahashi N, Saikawa T, et al. Diminished expression of sarcoplasmic reticulum Ca(2+)-ATPase and ryanodine sensitive Ca(2+)Channel mRNA in streptozotocin-induced diabetic rat heart. J Mol Cell Cardiol 2000; 32: 655–664.
- 24McCrossan ZA, Billeter R, White E. Transmural changes in size, contractile and electrical properties of SHR left ventricular myocytes during compensated hypertrophy. Cardiovasc Res 2004; 63: 283–292.
- 25Fowler MR, Naz JR, Graham MD, et al. Decreased Ca2+ extrusion via Na+/Ca2+ exchange in epicardial left ventricular myocytes during compensated hypertrophy. Am J Physiol Heart Circ Physiol 2005; 288: H2431–H2438.
- 26Casis O, Gallego M, Iriarte M, et al. Effects of diabetic cardiomyopathy on regional electrophysiologic characteristics of rat ventricle. Diabetologia 2000; 43: 101–109.
- 27Smail MM, Qureshi MA, Shmygol A, et al. Regional effects of streptozotocin-induced diabetes on shortening and calcium transport in epicardial and endocardial myocytes from rat left ventricle. Physiol Rep 2016; 4: e13034.
- 28Al Kury L, Sydorenko V, Smail MMA, et al. Voltage dependence of the Ca(2+) transient in endocardial and epicardial myocytes from the left ventricle of Goto-Kakizaki type 2 diabetic rats. Mol Cell Biochem 2018; 446: 25–33.
- 29Szkudelski T. Streptozotocin-nicotinamide-induced diabetes in the rat. Characteristics of the experimental model. Exp Biol Med 2012; 237: 481–490.
- 30Cheta D. Animal models of type I (insulin-dependent) diabetes mellitus. J Pediatr Endocrinol Metab 1998; 11: 11–19.
- 31Al Kury LT, Yang KH, Thayyullathil FT, et al. Effects of endogenous cannabinoid anandamide on cardiac Na(+)/Ca(2)(+) exchanger. Cell Calcium 2014; 55: 231–237.
- 32Bracken N, Howarth FC, Singh J. Effects of streptozotocin-induced diabetes on contraction and calcium transport in rat ventricular cardiomyocytes. Ann N Y Acad Sci 2006; 1084: 208–222.
- 33Yaras N, Ugur M, Ozdemir S, et al. Effects of diabetes on ryanodine receptor Ca release channel (RyR2) and Ca2+ homeostasis in rat heart. Diabetes 2005; 54: 3082–3088.
- 34Arikawa M, Takahashi N, Kira T, et al. Enhanced inhibition of L-type calcium currents by troglitazone in streptozotocin-induced diabetic rat cardiac ventricular myocytes. Br J Pharmacol 2002; 136: 803–810.
- 35Moore CJ, Shao CH, Nagai R, et al. Malondialdehyde and 4-hydroxynonenal adducts are not formed on cardiac ryanodine receptor (RyR2) and sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) in diabetes. Mol Cell Biochem 2013; 376: 121–135.
- 36Hamouda NN, Qureshi MA, Alkaabi JM, et al. Reduction in the amplitude of shortening and Ca(2+) transient by phlorizin and quercetin-3-O-glucoside in ventricular myocytes from streptozotocin-induced diabetic rats. Physiol Res 2016; 65: 239–250.
- 37Yaras N, Bilginoglu A, Vassort G, et al. Restoration of diabetes-induced abnormal local Ca2+ release in cardiomyocytes by angiotensin II receptor blockade. Am J Physiol Heart Circ Physiol 2007; 292: H912–H920.
- 38Lee MJ, Lee HS, Park SD, et al. Leonurus sibiricus herb extract suppresses oxidative stress and ameliorates hypercholesterolemia in C57BL/6 mice and TNF-alpha induced expression of adhesion molecules and lectin-like oxidized LDL receptor-1 in human umbilical vein endothelial cells. Biosci Biotechnol Biochem 2010; 74: 279–284.
- 39Lacombe VA, Viatchenko-Karpinski S, Terentyev D, et al. Mechanisms of impaired calcium handling underlying subclinical diastolic dysfunction in diabetes. Am J Physiol Regul Integr Comp Physiol 2007; 293: R1787–R1797.
- 40Zhang L, Ward ML, Phillips AR, et al. Protection of the heart by treatment with a divalent-copper-selective chelator reveals a novel mechanism underlying cardiomyopathy in diabetic rats. Cardiovasc Diabetol 2013; 12: 123.
- 41Kohajda Z, Farkas-Morvay N, Jost N, et al. The effect of a novel highly selective inhibitor of the sodium/calcium exchanger (NCX) on cardiac arrhythmias in in vitro and in vivo experiments. PLoS One 2016; 11: e0166041.
- 42Howarth FC, Adem A, Adeghate EA, et al. Distribution of atrial natriuretic peptide and its effects on contraction and intracellular calcium in ventricular myocytes from streptozotocin-induced diabetic rat. Peptides 2005; 26: 691–700.
- 43Gilca GE, Stefanescu G, Badulescu O, et al. Diabetic cardiomyopathy: current approach and potential diagnostic and therapeutic targets. J Diabetes Res 2017; 2017: 1310265.
- 44Bidasee KR, Nallani K, Yu Y, et al. Chronic diabetes increases advanced glycation end products on cardiac ryanodine receptors/calcium-release channels. Diabetes 2003; 52: 1825–1836.
- 45Naqvi RU, Macleod KT. Effect of hypertrophy on mechanisms of relaxation in isolated cardiac myocytes from guinea pig. Am J Physiol. 1994; 267(5 Pt 2): H1851–H1861.
- 46Brooksby P, Levi AJ, Jones JV. Investigation of the mechanisms underlying the increased contraction of hypertrophied ventricular myocytes isolated from the spontaneously hypertensive rat. Cardiovasc Res 1993; 27: 1268–1277.
- 47Sipido KR, Volders PG, de Groot SH, et al. Enhanced Ca(2+) release and Na/Ca exchange activity in hypertrophied canine ventricular myocytes: potential link between contractile adaptation and arrhythmogenesis. Circulation 2000; 102: 2137–2144.
- 48Salem KA, Qureshi MA, Sydorenko V, et al. Effects of exercise training on excitation-contraction coupling and related mRNA expression in hearts of Goto-Kakizaki type 2 diabetic rats. Mol Cell Biochem 2013; 380: 83–96.
- 49Currie S, Quinn FR, Sayeed RA, et al. Selective down-regulation of sub-endocardial ryanodine receptor expression in a rabbit model of left ventricular dysfunction. J Mol Cell Cardiol 2005; 39: 309–317.
- 50Igarashi-Saito K, Tsutsui H, Takahashi M, et al. Endocardial versus epicardial differences of sarcoplasmic reticulum Ca2+-ATPase gene expression in the canine failing myocardium. Basic Res Cardiol 1999; 94: 267–273.
- 51Xiong W, Tian Y, DiSilvestre D, et al. Transmural heterogeneity of Na+-Ca2+ exchange: evidence for differential expression in normal and failing hearts. Circ Res 2005; 97: 207–209.
