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Effects of streptozotocin-induced diabetes on action potentials in the sinoatrial node compared with other regions of the rat heart

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Abstract

In vivo biotelemetry studies have demonstrated that heart rate (HR) is progressively and rapidly reduced after administration of streptozotocin (STZ) and that the reduction in HR can be partially normalized with insulin replacement. Reductions in HR have also been reported in isolated perfused heart and superfused right atrial preparations suggesting that intrinsic defects in the heart are at least partly responsible for the bradycardia. The regional effects of STZ-induced diabetes mellitus (DM) on action potentials (APs) in the sinoatrial node (SAN), right and left atria and ventricles have been compared in the spontaneously beating Langendorff perfused rat heart 10–12 weeks after treatment. HR was significantly reduced in STZ-induced diabetic rat heart (174 ± 9 BPM) compared to controls (241 ± 12 BPM). The duration of AP repolarization at 50% and 70% from peak AP was significantly prolonged in SAN, right atrium and right ventricle from STZ-induced diabetic rat compared to age-matched controls. In the SAN AP duration (APD) at 50% and 70% were 51.7 ± 2.2 and 59.5 ± 2.3 ms in diabetic rat heart compared to 45.2 ± 1.7 and 50.0 ± 1.6 ms in controls, respectively. In contrast APD at 50% and 70% were not significantly altered in the left atrium and left ventricle. Regional defects in the expression and/or electrophysiology of SAN ion channels, and in particular those involved in AP repolarization, might underlie heart rhythm disturbances in the STZ-induced DM rat.

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References

  1. Amos AF, McCarty DJ, Zimmet P (1997) The rising global burden of diabetes and its complications: Estimates and projections to the year 2010. Diabetic Med 14:S7–S85

    Article  Google Scholar 

  2. Dhalla NS, Pierce GN, Innes IR, Beamish RE (1985) Pathogenesis of cardiac dysfunction in diabetes mellitus. Can J␣Cardiol 1:263–281

    PubMed  CAS  Google Scholar 

  3. Veglio M, Chinaglia A, Cavallo PP (2000) The clinical utility of QT interval assessment in diabetes. Diabetes Nutr Metab 13:356–365

    PubMed  CAS  Google Scholar 

  4. Linnemann B, Janka HU (2003) Prolonged QTc interval and elevated heart rate identify the type 2 diabetic patient at high risk for cardiovascular death. The Bremen Diabetes Study. Exp Clin Endocrinol Diabetes 111:215–222

    Article  PubMed  CAS  Google Scholar 

  5. Podlaha R, Falk A (1992) The prevalence of diabetes mellitus and other risk factors of atherosclerosis in bradycardia requiring pacemaker treatment. Horm Metab Res Suppl 26:84–87

    PubMed  CAS  Google Scholar 

  6. Dai S, Thompson KH, McNeill JH (1994) One-year treatment of streptozotocin-induced diabetic rats with vanadyl sulphate. Pharmacol Toxicol 74:101–109

    Article  PubMed  CAS  Google Scholar 

  7. Howarth FC, Qureshi MA, White E (2002) Effects of hyperosmotic shrinking on ventricular myocyte shortening and intracellular Ca(2+) in streptozotocin-induced diabetic rats. Pflügers Arch 444:446–451

    Article  PubMed  CAS  Google Scholar 

  8. Howarth FC, Jacobson M, Naseer O, Adeghate E (2005) Short-term effects of streptozotocin-induced diabetes on the electrocardiogram, physical activity and body temperature in rats. Exp Physiol 90:237–245

    Article  PubMed  CAS  Google Scholar 

  9. Howarth FC, Jacobson M, Shafiullah M, Adeghate E (2006) Effects of insulin treatment on heart rhythm, body temperature and physical activity in streptozotocin-induced diabetic rat. Clin Exp Pharmacol Physiol 33:327–331

    Article  PubMed  CAS  Google Scholar 

  10. Li XS, Tanz RD, Chang KS (1989) Effect of age and methacholine on the rate and coronary flow of isolated hearts of diabetic rats. Br J Pharmacol 97:1209–1217

    PubMed  CAS  Google Scholar 

  11. Hicks KK, Seifen E, Stimers JR, Kennedy RH (1998) Effects of streptozotocin-induced diabetes on heart rate, blood pressure and cardiac autonomic nervous control. J Auton Nerv Syst 69:21–30

    Article  PubMed  CAS  Google Scholar 

  12. Kofo-Abayomi A, Lucas PD (1988) A comparison between atria from control and streptozotocin-diabetic rats:the effects of dietary myoinositol. Br J Pharmacol 93:3–8

    PubMed  CAS  Google Scholar 

  13. Howarth FC, Qureshi MA (2006) Effects of carbenoxolone on heart rhythm, contractility and intracellular calcium in streptozotocin-induced diabetic rat. Mol Cell Biochem 289:21–9

    Article  PubMed  CAS  Google Scholar 

  14. Boyett MR, Honjo H, Kodama I (2000) The sinoatrial node, a heterogeneous pacemaker structure. Cardiovasc Res 47:658–687

    Article  PubMed  CAS  Google Scholar 

  15. Ishikawa T, Kajiwara H, Kurihara S (1999) Alterations in contractile properties and Ca2+ handling in streptozotocin-induced diabetic rat myocardium. Am J Physiol 277:H2185–H2194

    PubMed  CAS  Google Scholar 

  16. Loganathan R, Bilgen M, Al Hafez B, Smirnova IV (2006) Characterization of alterations in diabetic myocardial tissue using high resolution MRI. Int J Cardiovasc Imaging 22:81–90

    Article  PubMed  Google Scholar 

  17. Ruzicska E, Foldes G, Lako-Futo Z, Sarman B, Wellmann J, Szenasi G, Tulassay Z, Ruskoaho H, Toth M, Somogyi A (2004) Cardiac gene expression of natriuretic substances is altered in streptozotocin-induced diabetes during angiotensin II-induced pressure overload. J Hypertens 22:1191–1200

    Article  PubMed  CAS  Google Scholar 

  18. Grimm D, Jabusch HC, Kossmehl P, Huber M, Fredersdorf S, Griese DP, Kramer BK, Kromer EP (2002) Experimental diabetes and left ventricular hypertrophy:effects of beta-receptor blockade. Cardiovasc Pathol 11:229–237

    Article  PubMed  CAS  Google Scholar 

  19. Stadler K, Jenei V, Somogyi A, Jakus J (2004) Aminoguanidine prevents peroxynitrite production and cardiac hypertrophy in streptozotocin-induced diabetic rats. Orv Hetil 145:2491–2496

    PubMed  Google Scholar 

  20. Hajinazarian M, Cosio FG, Nahman NSJ, Mahan JD (1994) Angiotensin-converting enzyme inhibition partially prevents diabetic organomegaly. Am J Kidney Dis 23:105–117

    PubMed  CAS  Google Scholar 

  21. Marionneau C, Couette B, Liu J, Li H, Mangoni ME, Nargeot J, Lei M, Escande D, Demolombe S (2005) Specific pattern of ionic channel gene expression associated with pacemaker activity in the mouse heart. J Physiol 562:223–234

    Article  PubMed  CAS  Google Scholar 

  22. Satoh H (2003) Sino-atrial nodal cells of mammalian hearts:ionic currents and gene expression of pacemaker ionic channels. J Smooth Muscle Res 39:175–193

    Article  PubMed  Google Scholar 

  23. Shinagawa Y, Satoh H, Noma A (2000) The sustained inward current and inward rectifier K+ current in pacemaker cells dissociated from rat sinoatrial node. J Physiol 523:593–605

    Article  PubMed  CAS  Google Scholar 

  24. Satoh H (2005) Suppression of pacemaker activity by Ginkgo biloba extract and its main constituent, bilobalide in rat sino-atrial nodal cells. Life Sci 78:67–73

    Article  PubMed  CAS  Google Scholar 

  25. Satoh H (2000) Comparative actions of cibenzoline and disopyramide on I(Kr) and I(Ks) currents in rat sino-atrial nodal cells. Eur J Pharmacol 407:123–129

    Article  PubMed  CAS  Google Scholar 

  26. Shigematsu S, Maruyama T, Kiyosue T, Arita M (1994) Rate-dependent prolongation of action potential duration in single ventricular myocytes obtained from hearts of rats with streptozotocin-induced chronic diabetes sustained for 30–32 weeks. Heart Vessels 9:300–306

    Article  PubMed  CAS  Google Scholar 

  27. Yaras N, Turan B (2005) Interpretation of relevance of sodium-calcium exchange in action potential of diabetic rat heart by mathematical model. Mol Cell Biochem 269:121–129

    Article  PubMed  CAS  Google Scholar 

  28. Magyar J, Rusznak Z, Szentesi P, Szucs G, Kovacs L (1992) Action potentials and potassium currents in rat ventricular muscle during experimental diabetes. J Mol Cell Cardiol 24:841–853

    Article  PubMed  CAS  Google Scholar 

  29. Raimondi L, De Paoli P, Mannucci E, Lonardo G, Sartiani L, Banchelli G, Pirisino R, Mugelli A, Cerbai E (2004) Restoration of cardiomyocyte functional properties by angiotensin II receptor blockade in diabetic rats. Diabetes 53:1927–1933

    Article  PubMed  CAS  Google Scholar 

  30. Casis O, Gallego M, Iriarte M, Sanchez-Chapula JA (2000) Effects of diabetic cardiomyopathy on regional electrophysiologic characteristics of rat ventricle. Diabetologia 43:101–109

    Article  PubMed  CAS  Google Scholar 

  31. Shimoni Y, Firek L, Severson D, Giles W (1994) Short-term diabetes alters K+ currents in rat ventricular myocytes. Circ Res 74:620–628

    PubMed  CAS  Google Scholar 

  32. Jourdon P, Feuvray D (1993) Calcium and potassium currents in ventricular myocytes isolated from diabetic rats. J␣Physiol 470:411–429

    PubMed  CAS  Google Scholar 

  33. Bracken NK, Woodall AJ, Howarth FC, Singh J (2004) Voltage-dependence of contraction in streptozotocin-induced diabetic myocytes. Mol Cell Biochem 261:235–243

    Article  PubMed  CAS  Google Scholar 

  34. Pandit SV, Giles WR, Demir SS (2003) A mathematical model of the electrophysiological alterations in rat ventricular myocytes in type-I diabetes. Biophys J 84:832–841

    Article  PubMed  CAS  Google Scholar 

  35. Pacher P, Ungvari Z, Nanasi PP, Kecskemeti V (1999) Electrophysiological changes in rat ventricular and atrial myocardium at different stages of experimental diabetes. Acta Physiol Scand 166:7–13

    Article  PubMed  CAS  Google Scholar 

  36. Shimoni Y, Ewart HS, Severson D (1998) Type I and II models of diabetes produce different modifications of K+ currents in rat heart:role of insulin. J Physiol 507:485–496

    Article  PubMed  CAS  Google Scholar 

  37. Wang DW, Kiyosue T, Shigematsu S, Arita M (1995) Abnormalities of K+ and Ca2+ currents in ventricular myocytes from rats with chronic diabetes. Am J Physiol 269:H1288–H1296

    PubMed  CAS  Google Scholar 

  38. Shimoni Y, Severson D, Giles W (1995) Thyroid status and diabetes modulate regional differences in potassium currents in rat ventricle. J Physiol 488:673–688

    PubMed  CAS  Google Scholar 

  39. Qin D, Huang B, Deng L, El Adawi H, Ganguly K, Sowers JR, El Sherif N (2001) Downregulation of K(+) channel genes expression in type I diabetic cardiomyopathy. Biochem Biophys Res Commun 283:549–553

    Article  PubMed  CAS  Google Scholar 

  40. Choi KM, Zhong Y, Hoit BD, Grupp IL, Hahn H, Dilly KW, Guatimosim S, Lederer WJ, Matlib MA (2002) Defective intracellular Ca(2+) signaling contributes to cardiomyopathy in Type 1 diabetic rats. Am J Physiol 283:H1398–H1408

    CAS  Google Scholar 

  41. Wold LE, Ren J (2004) Streptozotocin directly impairs cardiac contractile function in isolated ventricular myocytes via a p38 map kinase-dependent oxidative stress mechanism. Biochem Biophys Res Commun 318:1066–1071

    Article  PubMed  CAS  Google Scholar 

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Acknowledgement

Thanks to Dr Andy James, University of Bristol, UK, for supplying the suction electrode.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine & Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, Abu Dhabi, UAE

    F. C. Howarth, R. Al-Sharhan, A. Al-Hammadi & M. A. Qureshi

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  1. F. C. Howarth
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  2. R. Al-Sharhan
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  3. A. Al-Hammadi
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  4. M. A. Qureshi
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Correspondence to F. C. Howarth.

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Howarth, F.C., Al-Sharhan, R., Al-Hammadi, A. et al. Effects of streptozotocin-induced diabetes on action potentials in the sinoatrial node compared with other regions of the rat heart. Mol Cell Biochem 300, 39–46 (2007). https://doi.org/10.1007/s11010-006-9366-5

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  • DOI: https://doi.org/10.1007/s11010-006-9366-5

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