Skip to main content
SpringerLink
Log in

Network Dynamics in Cardiac Electrophysiology

  • Chapter
  • First Online:
Systems Biology of Metabolic and Signaling Networks

Part of the book series: Springer Series in Biophysics ((BIOPHYSICS,volume 16))

Abstract

In a network perspective, the heart is a network of cells that are composed of subnetworks of genes, proteins, metabolites, and organelles. In this chapter, we provide an overview of the networks in the heart and a current understanding of the network dynamics in the context of cardiac electrophysiology. We first review current knowledge of the genetic, signaling, and metabolic networks in the heart and their links to arrhythmias. We then review the emergent properties from the mitochondrial and calcium release unit networks, the cellular dynamics arising from integrated subnetworks, and the electrical dynamics arising from the cellular networks to manifest as normal rhythms and arrhythmias. Finally, we discuss future challenges and how systems biology approaches can overcome these challenges to uncover the mechanisms of normal heart rhythms and arrhythmias.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Akar FG, Aon MA, Tomaselli GF, O’Rourke B (2005) The mitochondrial origin of postischemic arrhythmias. J Clin Invest 115(12):3527–3535

    PubMed  CAS  Google Scholar 

  • Aon MA, Cortassa S, Marban E, O’Rourke B (2003) Synchronized whole cell oscillations in mitochondrial metabolism triggered by a local release of reactive oxygen species in cardiac myocytes. J Biol Chem 278(45):44735–44744

    PubMed  CAS  Google Scholar 

  • Aon MA, Cortassa S, O’Rourke B (2004) Percolation and criticality in a mitochondrial network. Proc Natl Acad Sci USA 101(13):4447–4452

    PubMed  CAS  Google Scholar 

  • Arking DE, Junttila MJ, Goyette P, Huertas-Vazquez A, Eijgelsheim M, Blom MT, Newton-Cheh C, Reinier K, Teodorescu C, Uy-Evanado A, Carter-Monroe N, Kaikkonen KS, Kortelainen M-L, Boucher G, Lagace C, Moes A, Zhao X, Kolodgie F, Rivadeneira F, Hofman A, Witteman JCM, Uitterlinden AG, Marsman RF, Pazoki R, Bardai A, Koster RW, Dehghan A, Hwang S-J, Bhatnagar P, Post W, Hilton G, Prineas RJ, Li M, Kottgen A, Ehret G, Boerwinkle E, Coresh J, Kao WHL, Psaty BM, Tomaselli GF, Sotoodehnia N, Siscovick DS, Burke GL, Marban E, Spooner PM, Cupples LA, Jui J, Gunson K, Kesaniemi YA, Wilde AAM, Tardif J-C, O’Donnell CJ, Bezzina CR, Virmani R, Stricker BHC, Tan HL, Albert CM, Chakravarti A, Rioux JD, Huikuri HV, Chugh SS (2011) Identification of a sudden cardiac death susceptibility locus at 2q24.2 through Genome-Wide Association in European Ancestry Individuals. PLoS Genet 7(6):e1002158

    PubMed  CAS  Google Scholar 

  • Bak P (1997) How nature works: the science of self-organized criticality. Oxford University Press, New York

    Google Scholar 

  • Bak P, Tang C, Wiesenfeld K (1988) Self-organized criticality. Phys Rev A 38(1):364–374

    PubMed  Google Scholar 

  • Baudenbacher F, Schober T, Pinto JR, Sidorov VY, Hilliard F, Solaro RJ, Potter JD, Knollmann BC (2008) Myofilament Ca2+ sensitization causes susceptibility to cardiac arrhythmia in mice. J Clin Invest 118(12):3893–3903

    PubMed  CAS  Google Scholar 

  • Belevych AE, Terentyev D, Viatchenko-Karpinski S, Terentyeva R, Sridhar A, Nishijima Y, Wilson LD, Cardounel AJ, Laurita KR, Carnes CA, Billman GE, Gyorke S (2009) Redox modification of ryanodine receptors underlies calcium alternans in a canine model of sudden cardiac death. Cardiovasc Res 84(3):387–395

    PubMed  CAS  Google Scholar 

  • Bers DM (2002) Cardiac excitation–contraction coupling. Nature 415(6868):198–205

    PubMed  CAS  Google Scholar 

  • Bezzina CR, Pazoki R, Bardai A, Marsman RF, de Jong JS, Blom MT, Scicluna BP, Jukema JW, Bindraban NR, Lichtner P, Pfeufer A, Bishopric NH, Roden DM, Meitinger T, Chugh SS, Myerburg RJ, Jouven X, Kaab S, Dekker LR, Tan HL, Tanck MW, Wilde AA (2010) Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction. Nat Genet 42(8):688–691. doi:10.1038/ng.623

    PubMed  CAS  Google Scholar 

  • Bootman MD, Berridge MJ, Lipp P (1997) Cooking with calcium: the recipes for composing global signals from elementary events. Cell 91(3):367–373

    PubMed  CAS  Google Scholar 

  • Brady NR, Elmore SP, van Beek JJ, Krab K, Courtoy PJ, Hue L, Westerhoff HV (2004) Coordinated behavior of mitochondria in both space and time: a reactive oxygen species-activated wave of mitochondrial depolarization. Biophys J 87(3):2022–2034

    PubMed  CAS  Google Scholar 

  • Bridge JH, Ershler PR, Cannell MB (1999) Properties of Ca2+ sparks evoked by action potentials in mouse ventricular myocytes. J Physiol 518:469–478

    PubMed  CAS  Google Scholar 

  • Camelliti P, Devlin GP, Matthews KG, Kohl P, Green CR (2004a) Spatially and temporally distinct expression of fibroblast connexins after sheep ventricular infarction. Cardiovasc Res 62(2):415–425

    PubMed  CAS  Google Scholar 

  • Camelliti P, Green CR, LeGrice I, Kohl P (2004b) Fibroblast network in rabbit sinoatrial node: structural and functional identification of homogeneous and heterogeneous cell coupling. Circ Res 94(6):828–835

    PubMed  CAS  Google Scholar 

  • Cast I (1989) Effect of encainide and flecainide on mortality in a random trial of arrhythmia suppression after myocardial infarction. N Engl J Med 321:406–412

    Google Scholar 

  • Cerrone M, Napolitano C, Priori SG (2009) Catecholaminergic polymorphic ventricular tachycardia: a paradigm to understand mechanisms of arrhythmias associated to impaired Ca2+ regulation. Heart Rhythm 6(11):1652–1659

    PubMed  Google Scholar 

  • Cheng H, Lederer WJ (2008) Calcium sparks. Physiol Rev 88(4):1491–1545

    PubMed  CAS  Google Scholar 

  • Cheng H, Lederer WJ, Cannell MB (1993) Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle. Science 262(5134):740–744

    PubMed  CAS  Google Scholar 

  • Cheng H, Lederer MR, Lederer WJ, Cannell MB (1996) Calcium sparks and [Ca2+]i waves in cardiac myocytes. Am J Physiol 270(1 Pt 1):C148–159

    PubMed  CAS  Google Scholar 

  • Cortassa S, Aon MA, Marban E, Winslow RL, O’Rourke B (2003) An integrated model of cardiac mitochondrial energy metabolism and calcium dynamics. Biophys J 84(4):2734–2755

    PubMed  CAS  Google Scholar 

  • Cortassa S, Aon MA, Winslow RL, O’Rourke B (2004) A mitochondrial oscillator dependent on reactive oxygen species. Biophys J 87(3):2060–2073

    PubMed  CAS  Google Scholar 

  • Cortassa S, Aon MA, O’Rourke B, Jacques R, Tseng HJ, Marban E, Winslow RL (2006) A computational model integrating electrophysiology, contraction, and mitochondrial bioenergetics in the ventricular myocyte. Biophys J 91(4):1564–1589

    PubMed  CAS  Google Scholar 

  • Cui X, Rovetti RJ, Yang L, Garfinkel A, Weiss JN, Qu Z (2009) Period-doubling bifurcation in an array of coupled stochastically excitable elements subjected to global periodic forcing. Phys Rev Lett 103(4):044102–044104

    PubMed  Google Scholar 

  • Dash RK, Beard DA (2008) Analysis of cardiac mitochondrial Na+−Ca2+ exchanger kinetics with a biophysical model of mitochondrial Ca2+ handling suggests a 3:1 stoichiometry. J Physiol 586(13):3267–3285

    PubMed  CAS  Google Scholar 

  • De Giorgi F, Lartigue L, Ichas F (2000) Electrical coupling and plasticity of the mitochondrial network. Cell Calcium 28(5–6):365–370

    PubMed  Google Scholar 

  • Feist AM, Herrgard MJ, Thiele I, Reed JL, Palsson BO (2009) Reconstruction of biochemical networks in microorganisms. Nat Rev Microbiol 7(2):129–143. doi:10.1038/nrmicro1949

    PubMed  CAS  Google Scholar 

  • Florea SM, Blatter LA (2010) The role of mitochondria for the regulation of cardiac alternans. Front Physiol 1:141

    PubMed  CAS  Google Scholar 

  • Franzini-Armstrong C, Protasi F, Ramesh V (1999) Shape, size, and distribution of Ca(2+) release units and couplons in skeletal and cardiac muscles. Biophys J 77(3):1528–1539

    PubMed  CAS  Google Scholar 

  • Greenstein JL, Winslow RL (2011) Integrative systems models of cardiac excitation-contraction coupling. Circ Res 108(1):70–84

    PubMed  CAS  Google Scholar 

  • Grimm M, Ling H, Brown JH (2011) Crossing signals: relationships between beta-adrenergic stimulation and CaMKII activation. Heart Rhythm 8(8):1296–1298. doi:10.1016/j.hrthm.2011.02.027

    PubMed  Google Scholar 

  • Hashambhoy YL, Winslow RL, Greenstein JL (2009) CaMKII-induced shift in modal gating explains L-type Ca(2+) current facilitation: a modeling study. Biophys J 96(5):1770–1785. doi:10.1016/j.bpj.2008.11.055

    PubMed  CAS  Google Scholar 

  • Hashambhoy YL, Greenstein JL, Winslow RL (2010) Role of CaMKII in RyR leak, EC coupling and action potential duration: a computational model. J Mol Cell Cardiol 49(4):617–624

    PubMed  CAS  Google Scholar 

  • Hatano A, Okada J, Washio T, Hisada T, Sugiura S (2011) A three-dimensional simulation model of cardiomyocyte integrating excitation-contraction coupling and metabolism. Biophys J 101(11):2601–2610. doi:10.1016/j.bpj.2011.10.020

    PubMed  CAS  Google Scholar 

  • Hatano A, Okada J, Hisada T, Sugiura S (2012) Critical role of cardiac t-tubule system for the maintenance of contractile function revealed by a 3D integrated model of cardiomyocytes. J Biomech 45(5):815–823. doi:10.1016/j.jbiomech.2011.11.022

    PubMed  Google Scholar 

  • Hedley PL, Jørgensen P, Schlamowitz S, Moolman-Smook J, Kanters JK, Corfield VA, Christiansen M (2009) The genetic basis of Brugada syndrome: a mutation update. Hum Mutat 30(9):1256–1266

    PubMed  CAS  Google Scholar 

  • Honda HM, Korge P, Weiss JN (2005) Mitochondria and ischemia/reperfusion injury. Ann N Y Acad Sci 1047:248–258

    PubMed  CAS  Google Scholar 

  • Huke S, Knollmann BC (2010) Increased myofilament Ca2+−sensitivity and arrhythmia susceptibility. J Mol Cell Cardiol 48(5):824–833

    PubMed  CAS  Google Scholar 

  • Hund TJ, Rudy Y (2004) Rate dependence and regulation of action potential and calcium transient in a canine cardiac ventricular cell model. Circulation 110(20):3168–3174

    PubMed  CAS  Google Scholar 

  • Hund TJ, Decker KF, Kanter E, Mohler PJ, Boyden PA, Schuessler RB, Yamada KA, Rudy Y (2008) Role of activated CaMKII in abnormal calcium homeostasis and I(Na) remodeling after myocardial infarction: insights from mathematical modeling. J Mol Cell Cardiol 45(3): 420–428

    PubMed  CAS  Google Scholar 

  • Huser J, Wang YG, Sheehan KA, Cifuentes F, Lipsius SL, Blatter LA (2000) Functional coupling between glycolysis and excitation–contraction coupling underlies alternans in cat heart cells. J Physiol 524(Pt 3):795–806

    PubMed  CAS  Google Scholar 

  • Ivanov PC, Amaral LA, Goldberger AL, Havlin S, Rosenblum MG, Struzik ZR, Stanley HE (1999) Multifractality in human heartbeat dynamics. Nature 399(6735):461–465

    PubMed  CAS  Google Scholar 

  • Jafri MS, Kotulska M (2006) Modeling the mechanism of metabolic oscillations in ischemic cardiac myocytes. J Theor Biol 242(4):801–817

    Google Scholar 

  • Jeyaraj D, Haldar SM, Wan X, McCauley MD, Ripperger JA, Hu K, Lu Y, Eapen BL, Sharma N, Ficker E, Cutler MJ, Gulick J, Sanbe A, Robbins J, Demolombe S, Kondratov RV, Shea SA, Albrecht U, Wehrens XH, Rosenbaum DS, Jain MK (2012) Circadian rhythms govern cardiac repolarization and arrhythmogenesis. Nature 483(7387):96–99. doi:10.1038/nature10852

    PubMed  CAS  Google Scholar 

  • Katz AM (2011) Physiology of the heart, 5th edn. Lippincott Williams & Wilkins, Philadelphia, PA

    Google Scholar 

  • Keating MT, Sanguinetti MC (2001) Molecular and cellular mechanisms of cardiac arrhythmias. Cell 104(4):569–580

    PubMed  CAS  Google Scholar 

  • Kockskamper J, Zima AV, Blatter LA (2005) Modulation of sarcoplasmic reticulum Ca2+ release by glycolysis in cat atrial myocytes. J Physiol (Lond) 564(3):697–714

    Google Scholar 

  • Kurz FT, Aon MA, O’Rourke B, Armoundas AA (2010) Spatio-temporal oscillations of individual mitochondria in cardiac myocytes reveal modulation of synchronized mitochondrial clusters. Proc Natl Acad Sci USA 107(32):14315–14320

    PubMed  CAS  Google Scholar 

  • Lakatta EG, Maltsev VA, Bogdanov KY, Stern MD, Vinogradova TM (2003) Cyclic variation of intracellular calcium: a critical factor for cardiac pacemaker cell dominance. Circ Res 92(3):e45–50

    PubMed  CAS  Google Scholar 

  • Lakatta EG, Maltsev VA, Vinogradova TM (2010) A coupled system of intracellular Ca2+ clocks and surface membrane voltage clocks controls the timekeeping mechanism of the heart’s pacemaker. Circ Res 106(4):659–673

    PubMed  CAS  Google Scholar 

  • Lukyanenko V, Gyorke S (1999) Ca2+ sparks and Ca2+ waves in saponin-permeabilized rat ventricular myocytes. J Physiol 521(Pt 3):575–585

    PubMed  CAS  Google Scholar 

  • Maltsev AV, Maltsev VA, Mikheev M, Maltseva LA, Sirenko SG, Lakatta EG, Stern MD (2011) Synchronization of stochastic Ca(2)(+) release units creates a rhythmic Ca(2)(+) clock in cardiac pacemaker cells. Biophys J 100(2):271–283

    PubMed  CAS  Google Scholar 

  • Marchant JS, Parker I (2001) Role of elementary Ca(2+) puffs in generating repetitive Ca(2+) oscillations. EMBO J 20(1–2):65–76

    PubMed  CAS  Google Scholar 

  • Matsuoka S, Sarai N, Jo H, Noma A (2004) Simulation of ATP metabolism in cardiac excitation-contraction coupling. Prog Biophys Mol Biol 85(2–3):279–299

    PubMed  CAS  Google Scholar 

  • Moss AJ, Kass RS (2005) Long QT syndrome: from channels to cardiac arrhythmias. J Clin Invest 115(8):2018–2024

    PubMed  CAS  Google Scholar 

  • Napolitano C, Bloise R, Monteforte N, Priori SG (2012) Sudden cardiac death and genetic ion channelopathies. Circulation 125(16):2027–2034. doi:10.1161/circulationaha.111.055947

    PubMed  Google Scholar 

  • Nivala M, Korge P, Nivala M, Weiss JN, Qu Z (2011) Linking flickering to waves and whole-cell oscillations in a mitochondrial network model. Biophys J 101(9):2102–2111. doi:10.1016/j.bpj.2011.09.038

    PubMed  CAS  Google Scholar 

  • Nivala M, de Lange E, Rovetti R, Qu Z (2012a) Computational modeling and numerical methods for spatiotemporal calcium cycling in ventricular myocytes. Front Physiol 3:114. doi:10.3389/fphys.2012.00114

    PubMed  Google Scholar 

  • Nivala M, Ko CY, Nivala M, Weiss JN, Qu Z (2012b) Criticality in intracellular calcium signaling in cardiac myocytes. Biophys J 102(11):2433–2442. doi:10.1016/j.bpj.2012.05.001

    PubMed  CAS  Google Scholar 

  • Noble D (1962) A modification of the Hodgkin-Huxley equations applicable to Purkinje fibre action and pace-maker potentials. J Physiol 160:317–352

    PubMed  CAS  Google Scholar 

  • Noble D, Rudy Y (2001) Models of cardiac ventricular action potentials: iterative interaction between experiment and simulation. Philos Trans R Soc Lond Ser A 359(1783):1127–1142. doi:10.1098/rsta.2001.0820

    Google Scholar 

  • O’Rourke B, Ramza BM, Marban E (1994) Oscillations of membrane current and excitability driven by metabolic oscillations in heart cells. Science 265(5174):962–966

    PubMed  Google Scholar 

  • Peters NS, Wit AL (1998) Myocardial architecture and ventricular arrhythmogenesis. Circulation 97(17):1746–1754

    PubMed  CAS  Google Scholar 

  • Ponard JG, Kondratyev AA, Kucera JP (2007) Mechanisms of intrinsic beating variability in cardiac cell cultures and model pacemaker networks. Biophys J 92(10):3734–3752

    PubMed  CAS  Google Scholar 

  • Pouvreau S (2010) Superoxide flashes in mouse skeletal muscle are produced by discrete arrays of active mitochondria operating coherently. PLoS One 5(9)

    Google Scholar 

  • Prosser BL, Ward CW, Lederer WJ (2011) X-ROS signaling: rapid mechano-chemo transduction in heart. Science 333(6048):1440–1445. doi:10.1126/science.1202768

    PubMed  CAS  Google Scholar 

  • Qu Z (2011) Chaos in the genesis and maintenance of cardiac arrhythmias. Prog Biophys Mol Biol 105(3):247–257

    PubMed  Google Scholar 

  • Qu Z, Weiss JN (2006) Dynamics and cardiac arrhythmias. J Cardiovasc Electrophysiol 17:1042–1049

    PubMed  Google Scholar 

  • Qu Z, Garfinkel A, Weiss JN, Nivala M (2011) Multi-scale modeling in biology: how to bridge the gaps between scales? Prog Biophys Mol Biol 107:21–31

    PubMed  Google Scholar 

  • Rovetti R, Cui X, Garfinkel A, Weiss JN, Qu Z (2010) Spark-induced sparks as a mechanism of intracellular calcium alternans in cardiac myocytes. Circ Res 106:1582–1591. doi:10.1161/circresaha.109.213975

    PubMed  CAS  Google Scholar 

  • Sanguinetti MC, Tristani-Firouzi M (2006) hERG potassium channels and cardiac arrhythmia. Nature 440(7083):463–469

    PubMed  CAS  Google Scholar 

  • Sanguinetti MC, Jiang C, Curran ME, Keating MT (1995) A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell 81(2):299–307

    PubMed  CAS  Google Scholar 

  • Sato D, Xie LH, Sovari AA, Tran DX, Morita N, Xie F, Karagueuzian H, Garfinkel A, Weiss JN, Qu Z (2009) Synchronization of chaotic early afterdepolarizations in the genesis of cardiac arrhythmias. Proc Natl Acad Sci USA 106(9):2983–2988

    PubMed  CAS  Google Scholar 

  • Saucerman JJ, Bers DM (2008) Calmodulin mediates differential sensitivity of CaMKII and calcineurin to local Ca2+ in cardiac myocytes. Biophys J 95(10):4597–4612

    PubMed  CAS  Google Scholar 

  • Saucerman JJ, Brunton LL, Michailova AP, McCulloch AD (2003) Modeling beta-adrenergic control of cardiac myocyte contractility in silico. J Biol Chem 278(48):47997–48003

    PubMed  CAS  Google Scholar 

  • Saucerman JJ, Healy SN, Belik ME, Puglisi JL, McCulloch AD (2004) Proarrhythmic consequences of a KCNQ1 AKAP-binding domain mutation: computational models of whole cells and heterogeneous tissue. Circ Res 95(12):1216–1224

    PubMed  CAS  Google Scholar 

  • Skupin A, Kettenmann H, Winkler U, Wartenberg M, Sauer H, Tovey SC, Taylor CW, Falcke M (2008) How does intracellular Ca2+ oscillate: by chance or by the clock? Biophys J 94(6):2404–2411

    PubMed  CAS  Google Scholar 

  • Skupin A, Kettenmann H, Falcke M (2010) Calcium signals driven by single channel noise. PLoS Comput Biol 6(8):e1000870. doi:10.1371/journal.pcbi.1000870

    PubMed  Google Scholar 

  • Soeller C, Cannell MB (1999) Examination of the transverse tubular system in living cardiac rat myocytes by 2-photon microscopy and digital image–processing techniques. Circ Res 84(3):266–275

    PubMed  CAS  Google Scholar 

  • Soltis AR, Saucerman JJ (2010) Synergy between CaMKII substrates and beta-adrenergic signaling in regulation of cardiac myocyte Ca(2+) handling. Biophys J 99(7):2038–2047. doi:10.1016/j.bpj.2010.08.016

    PubMed  CAS  Google Scholar 

  • Spach MS, Heidlage JF (1995) The stochastic nature of cardiac propagation at a microscopic level—electrical description of myocardial architecture and its application to conduction. Circ Res 76(3):366–380

    PubMed  CAS  Google Scholar 

  • Stanley HE (1971) Introduction to phase transitions and critical phenomena. Oxford University Press, London

    Google Scholar 

  • Stanley HE (1999) Scaling, universality, and renormalization: three pillars of modern critical phenomena. Rev Mod Phys 71:S358–S366

    CAS  Google Scholar 

  • Swaminathan PD, Purohit A, Hund TJ, Anderson ME (2012) Calmodulin-dependent protein kinase II: linking heart failure and arrhythmias. Circ Res 110(12):1661–1677. doi:10.1161/CIRCRESAHA.111.243956

    PubMed  CAS  Google Scholar 

  • ter Keurs HEDJ, Boyden PA (2007) Calcium and arrhythmogenesis. Physiol Rev 87(2):457–506

    PubMed  Google Scholar 

  • ter Keurs HEDJ, Shinozaki T, Zhang YM, Zhang ML, Wakayama Y, Sugai Y, Kagaya Y, Miura M, Boyden PA, Stuyvers BDM, Landesberg A (2008) Sarcomere mechanics in uniform and non-uniform cardiac muscle: a link between pump function and arrhythmias. Prog Biophys Mol Biol 97(2–3):312–331

    PubMed  Google Scholar 

  • Thiffault C, Bennett JP Jr (2005) Cyclical mitochondrial deltapsiM fluctuations linked to electron transport, F0F1 ATP-synthase and mitochondrial Na+/Ca2+ exchange are reduced in Alzheimer’s disease cybrids. Mitochondrion 5(2):109–119

    PubMed  CAS  Google Scholar 

  • Turcotte DL, Rundle JB (2002) Self-organized complexity in the physical, biological, and social sciences. Proc Natl Acad Sci USA 99(Suppl 1):2463–2465

    PubMed  Google Scholar 

  • Waldo AL, Camm AJ, deRuyter H, Friedman PL, Macneil DJ, Pauls JF, Pitt B, Pratt CM, Schwartz PJ, Veltri EP (1996) Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. Lancet 348:7–12

    PubMed  CAS  Google Scholar 

  • Wang Y (2007) Mitogen-activated protein kinases in heart development and diseases. Circulation 116(12):1413–1423

    PubMed  CAS  Google Scholar 

  • Wang W, Fang H, Groom L, Cheng A, Zhang W, Liu J, Wang X, Li K, Han P, Zheng M, Yin J, Wang W, Mattson MP, Kao JP, Lakatta EG, Sheu SS, Ouyang K, Chen J, Dirksen RT, Cheng H (2008) Superoxide flashes in single mitochondria. Cell 134(2):279–290

    PubMed  CAS  Google Scholar 

  • Weiss JN, Karma A, Maclellan WR, Deng M, Rau CD, Rees CM, Wang J, Wisniewski N, Eskin E, Horvath S, Qu Z, Wang Y, Lusis AJ (2012) “Good enough solutions” and the genetics of complex diseases. Circ Res 111(4):493–504. doi:10.1161/CIRCRESAHA.112.269084

    PubMed  CAS  Google Scholar 

  • Wier WG, ter Keurs HE, Marban E, Gao WD, Balke CW (1997) Ca2+ ‘sparks’ and waves in intact ventricular muscle resolved by confocal imaging. Circ Res 81(4):462–469

    PubMed  CAS  Google Scholar 

  • Wu F, Yang F, Vinnakota KC, Beard DA (2007) Computer modeling of mitochondrial tricarboxylic acid cycle, oxidative phosphorylation, metabolite transport, and electrophysiology. J Biol Chem 282(34):24525–24537

    PubMed  CAS  Google Scholar 

  • Xie L-H, Chen F, Karagueuzian HS, Weiss JN (2009) Oxidative stress-induced afterdepolarizations and calmodulin kinase II signaling. Circ Res 104(1):79–86. doi:10.1161/circresaha.108.183475

    PubMed  CAS  Google Scholar 

  • Yang JH, Yang L, Qu Z, Weiss JN (2008) Glycolytic oscillations in isolated rabbit ventricular myocytes. J Biol Chem 283(52):36321–36327

    PubMed  CAS  Google Scholar 

  • Yang L, Korge P, Weiss JN, Qu Z (2010) Mitochondrial oscillations and waves in cardiac myocytes: insights from computational models. Biophys J 98(8):1428–1438

    PubMed  CAS  Google Scholar 

  • Zhou L, O’Rourke B (2012) Cardiac mitochondrial network excitability: insights from computational analysis. Am J Physiol Heart Circ Physiol 302(11):H2178–2189. doi:10.1152/ajpheart.01073.2011

    PubMed  CAS  Google Scholar 

  • Zhou L, Salem JE, Saidel GM, Stanley WC, Cabrera ME (2005a) Mechanistic model of cardiac energy metabolism predicts localization of glycolysis to cytosolic subdomain during ischemia. Am J Physiol Heart Circ Physiol 288(5):H2400–2411

    PubMed  CAS  Google Scholar 

  • Zhou L, Stanley WC, Saidel GM, Yu X, Cabrera ME (2005b) Regulation of lactate production at the onset of ischaemia is independent of mitochondrial NADH/NAD+: insights from in silico studies. J Physiol 569(Pt 3):925–937

    PubMed  CAS  Google Scholar 

  • Zhou L, Aon MA, Almas T, Cortassa S, Winslow RL, O’Rourke B (2010) A reaction–diffusion model of ROS-induced ROS release in a mitochondrial network. PLoS Comput Biol 6(1):e1000657

    PubMed  Google Scholar 

  • Zhou L, Aon MA, Liu T, O’Rourke B (2011) Dynamic modulation of Ca2+ sparks by mitochondrial oscillations in isolated guinea pig cardiomyocytes under oxidative stress. J Mol Cell Cardiol 51(5):632–639. doi:10.1016/j.yjmcc.2011.05.007

    PubMed  CAS  Google Scholar 

  • Zipes DP, Rubart M (2006) Neural modulation of cardiac arrhythmias and sudden cardiac death. Heart Rhythm 3(1):108–113. doi:10.1016/j.hrthm.2005.09.021

    PubMed  Google Scholar 

  • Zipes DP, Wellens HJ (1998) Sudden cardiac death. Circulation 98(21):2334–2351

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine (Cardiology), David Geffen School of Medicine, University of California, A2-237 CHS, 650 Charles E. Young Drive South, Los Angeles, CA, 90095, USA

    Zhilin Qu

Authors
  1. Zhilin Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhilin Qu .

Editor information

Editors and Affiliations

  1. School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA

    Miguel A. Aon

  2. Laboratory of Fundamental and Applied Bi, Inserm U1055 and University Joseph Fourier, Grenoble, Grenoble cedex 9, France

    Valdur Saks

  3. Laboratory of Fundamental and Applied Bi, Inserm U1055 and University Joseph Fourier, Grenoble, Grenoble cedex 9, France

    Uwe Schlattner

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Qu, Z. (2014). Network Dynamics in Cardiac Electrophysiology. In: Aon, M., Saks, V., Schlattner, U. (eds) Systems Biology of Metabolic and Signaling Networks. Springer Series in Biophysics, vol 16. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38505-6_10

Download citation

Publish with us

Policies and ethics

Search

Navigation