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The architecture and function of cardiac dyads

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Abstract

Cardiac excitation-contraction (EC) coupling, which links plasma membrane depolarization to activation of cardiomyocyte contraction, occurs at dyads, the nanoscopic microdomains formed by apposition of transverse (T)-tubules and junctional sarcoplasmic reticulum (jSR). In a dyadic junction, EC coupling occurs through Ca2+-induced Ca2+ release. Membrane depolarization opens voltage-gated L-type Ca2+ channels (LTCCs) in the T-tubule. The resulting influx of extracellular Ca2+ into the dyadic cleft opens Ca2+ release channels known as ryanodine receptors (RYRs) in the jSR, leading to the rapid increase in cytosolic Ca2+ that triggers sarcomere contraction. The efficacy of LTCC-RYR communication greatly affects a myriad of downstream intracellular signaling events, and it is controlled by many factors, including T-tubule and jSR structure, spatial distribution of ion channels, and regulatory proteins that closely regulate the activities of channels within dyads. Alterations in dyad architecture and/or channel activity are seen in many types of heart disease. This review will focus on the current knowledge regarding cardiac dyad structure and function, their alterations in heart failure, and new approaches to study the composition and function of dyads.

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References

  • Acsai K, Antoons G, Livshitz L et al (2011) Microdomain [Ca2+] near ryanodine receptors as reported by L-type Ca2+ and Na+/Ca2+ exchange currents. J Physiol 589:2569–2583

    CAS  PubMed  PubMed Central  Google Scholar 

  • Baddeley D, Jayasinghe ID, Lam L et al (2009) Optical single-channel resolution imaging of the ryanodine receptor distribution in rat cardiac myocytes. Proc Natl Acad Sci 106:22275–22280

    CAS  PubMed  Google Scholar 

  • Bers D (2001) Excitation-contraction coupling and cardiac contractile force. Springer Science & Business Media

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

    CAS  PubMed  Google Scholar 

  • Bongianino R, Denegri M, Mazzanti A et al (2017) Allele-specific silencing of mutant mRNA rescues ultrastructural and arrhythmic phenotype in mice carriers of the R4496C mutation in the ryanodine receptor gene (RYR2). Circ Res 121:525–536

    CAS  PubMed  Google Scholar 

  • Brandt N (1985) Identification of two populations of cardiac microsomes with nitrendipine receptors: correlation of the distribution of dihydropyridine receptors with organelle specific markers. Arch Biochem Biophys 242:306–319

    CAS  PubMed  Google Scholar 

  • Brochet DXP, Yang D, Di Maio A et al (2005) Ca2+ blinks: rapid nanoscopic store calcium signaling. Proc Natl Acad Sci U S A 102:3099–3104

    CAS  PubMed  PubMed Central  Google Scholar 

  • Burton RAB, Rog-Zielinska EA, Corbett AD et al (2017) Caveolae in rabbit ventricular myocytes: distribution and dynamic diminution after cell isolation. Biophys J 113:1047–1059

    CAS  PubMed  PubMed Central  Google Scholar 

  • Caldwell JL, Smith CER, Taylor RF et al (2014) Dependence of cardiac transverse tubules on the BAR domain protein amphiphysin II (BIN-1). Circ Res 115:986–996

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cannell MB, Cheng H, Lederer WJ (1994) Spatial non-uniformities in [Ca2+]i during excitation-contraction coupling in cardiac myocytes. Biophys J 67:1942–1956

  • Cannell MB, Crossman DJ, Soeller C (2006) Effect of changes in action potential spike configuration, junctional sarcoplasmic reticulum micro-architecture and altered t-tubule structure in human heart failure. J Muscle Res Cell Motil 27:297–306

    CAS  PubMed  Google Scholar 

  • Cannell MB, Kong CHT, Imtiaz MS, Laver DR (2013) Control of sarcoplasmic reticulum Ca2+ release by stochastic RyR gating within a 3D model of the cardiac dyad and importance of induction decay for CICR termination. Biophys J 104:2149–2159

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen B, Guo A, Zhang C et al (2013) Critical roles of junctophilin-2 in T-tubule and excitation–contraction coupling maturation during postnatal development. Cardiovasc Res 100:54–62

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Cheng H, Lederer MR, Lederer WJ, Cannell MB (1996) Calcium sparks and [Ca2+]i waves in cardiac myocytes. Am J Phys Cell Phys 270:C148–C159

  • Chopra N, Yang T, Asghari P et al (2009) Ablation of triadin causes loss of cardiac Ca2+ release units, impaired excitation–contraction coupling, and cardiac arrhythmias. Proc Natl Acad Sci U S A 106:7636–7641

    CAS  PubMed  PubMed Central  Google Scholar 

  • Connell P, Word TA, Wehrens XHT (2020) Targeting pathological leak of ryanodine receptors: preclinical progress and the potential impact on treatments for cardiac arrhythmias and heart failure. Expert Opin Ther Targets 24:25–36

    CAS  PubMed  Google Scholar 

  • Crossman DJ, Young AA, Ruygrok PN et al (2015) T-tubule disease: relationship between t-tubule organization and regional contractile performance in human dilated cardiomyopathy. J Mol Cell Cardiol 84:170–178

    CAS  PubMed  PubMed Central  Google Scholar 

  • Crossman DJ, Shen X, Jüllig M et al (2017) Increased collagen within the transverse tubules in human heart failure. Cardiovasc Res 113:879–891

    CAS  PubMed  Google Scholar 

  • Denegri M, Avelino-Cruz JE, Boncompagni S et al (2012) Viral gene transfer rescues arrhythmogenic phenotype and ultrastructural abnormalities in adult calsequestrin-null mice with inherited arrhythmias. Circ Res 110:663–668

    CAS  PubMed  Google Scholar 

  • Fabiato A, Fabiato F (1975) Contractions induced by a calcium-triggered release of calcium from the sarcoplasmic reticulum of single skinned cardiac cells. J Physiol 249:469–495

    CAS  PubMed  PubMed Central  Google Scholar 

  • Feng W, Liu C, Spinozzi S et al (2020) Identifying the cardiac dyad proteome in vivo by a BioID2 knock-in strategy. Circulation 141:940–942

    PubMed  Google Scholar 

  • Forssmann WG, Girardier L (1970) A study of the T system in rat heart. J Cell Biol 44:1–19

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fowler ED, Wang N, Hezzell M et al (2020) Arrhythmogenic late Ca2 sparks in failing heart cells and their control by action potential configuration. Proc Natl Acad Sci 117:2687–2692

    CAS  PubMed  Google Scholar 

  • Franzini-Armstrong C, Porter KR (1964) Sarcolemmal invaginations constituting the T system in fish muscle fibers. J Cell Biol 22:675–696

    CAS  PubMed  PubMed Central  Google Scholar 

  • Franzini-Armstrong C, Protasi F, Ramesh V (1999) Shape, size, and distribution of Ca2+ release units and couplons in skeletal and cardiac muscles. Biophys J 77:1528–1539

    CAS  PubMed  PubMed Central  Google Scholar 

  • Franzini-Armstrong C, Protasi F, Tijskens P (2005) The assembly of calcium release units in cardiac muscle. Ann N Y Acad Sci 1047:76–85

    CAS  PubMed  Google Scholar 

  • Frisk M, Ruud M, Espe EKS et al (2016) Elevated ventricular wall stress disrupts cardiomyocyte t-tubule structure and calcium homeostasis. Cardiovasc Res 112:443–451

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fu Y, Hong T (2016) BIN1 regulates dynamic t-tubule membrane. Biochim Biophys Acta 1863:1839–1847

    CAS  PubMed  Google Scholar 

  • Gergs U, Berndt T, Buskase J et al (2007) On the role of junctin in cardiac Ca2+ handling, contractility, and heart failure. Am J Physiol Heart Circ Physiol 293:H728–H734

    CAS  PubMed  Google Scholar 

  • Gomez AM (1997) Defective excitation-contraction coupling in experimental cardiac hypertrophy and heart failure. Science 276:800–806

    CAS  PubMed  Google Scholar 

  • Guo Y, Pu WT (2018) Genetic mosaics for greater precision in cardiovascular research. Circ Res 123:27–29

    CAS  PubMed  PubMed Central  Google Scholar 

  • Guo Y, Pu WT (2020) Cardiomyocyte maturation: new phase in development. Circ Res 126:1086–1106

    CAS  PubMed  Google Scholar 

  • Guo A, Hall D, Zhang C et al (2015) Molecular determinants of calpain-dependent cleavage of junctophilin-2 protein in cardiomyocytes. J Biol Chem 290:17946–17955

    CAS  PubMed  PubMed Central  Google Scholar 

  • Guo Y, VanDusen NJ, Zhang L et al (2017) Analysis of cardiac myocyte maturation using CASAAV, a platform for rapid dissection of cardiac myocyte gene function in vivo. Circ Res 120:1874–1888

    CAS  PubMed  PubMed Central  Google Scholar 

  • Guo A, Wang Y, Chen B et al (2018a) E-C coupling structural protein junctophilin-2 encodes a stress-adaptive transcription regulator. Science 362. https://doi.org/10.1126/science.aan3303

  • Guo Y, Jardin BD, Zhou P et al (2018b) Hierarchical and stage-specific regulation of murine cardiomyocyte maturation by serum response factor. Nat Commun 9:3837

    PubMed  PubMed Central  Google Scholar 

  • Guo Y, Jardin BD, Sethi I, et al (2019) Sarcomeres regulate cardiomyocyte maturation through MRTF-SRF signaling. bioRxiv. https://doi.org/10.1101/824185

  • Gyorke S, Fill M (1993) Ryanodine receptor adaptation: control mechanism of Ca2+-induced Ca2+ release in heart. Science 260:807–809

  • He J (2001) Reduction in density of transverse tubules and L-type Ca2 channels in canine tachycardia-induced heart failure. Cardiovasc Res 49:298–307

    CAS  PubMed  Google Scholar 

  • He W, Huang D, Guo S et al (2020) Association with SERCA2a directs phospholamban trafficking to sarcoplasmic reticulum from a nuclear envelope pool. J Mol Cell Cardiol 143:107–119

    CAS  PubMed  Google Scholar 

  • Heinzel FR, Bito V, Biesmans L et al (2008) Remodeling of T-tubules and reduced synchrony of Ca2 release in myocytes From chronically ischemic myocardium. Circ Res 102:338–346

    CAS  PubMed  Google Scholar 

  • Hong T, Shaw RM (2017) Cardiac T-tubule microanatomy and function. Physiol Rev 97:227–252

    PubMed  Google Scholar 

  • Hong T-T, Smyth JW, Gao D et al (2010) BIN1 Localizes the L-type calcium channel to cardiac T-tubules. PLoS Biol 8:e1000312

    PubMed  PubMed Central  Google Scholar 

  • Hong T-T, Smyth JW, Chu KY et al (2012) BIN1 is reduced and Cav1.2 trafficking is impaired in human failing cardiomyocytes. Heart Rhythm 9:812–820

    PubMed  Google Scholar 

  • Hong T, Yang H, Zhang S-S et al (2014) Cardiac BIN1 folds T-tubule membrane, controlling ion flux and limiting arrhythmia. Nat Med 20:624–632

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jorgensen AO, Shen AC, Daly P, MacLennan DH (1982) Localization of Ca2+ Mg2+ -ATPase of the sarcoplasmic reticulum in adult rat papillary muscle. J Cell Biol 93:883–892

  • Kaprielian RR, Stevenson S, Rothery SM et al (2000) Distinct patterns of dystrophin organization in myocyte sarcolemma and transverse tubules of normal and diseased human myocardium. Circulation 101:2586–2594

    CAS  PubMed  Google Scholar 

  • Knollmann BC (2010) A “rough” journey to the sarcoplasmic reticulum--implications of altered calsequestrin trafficking for cardiac arrhythmia. J Mol Cell Cardiol 49:554–555

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kolstad TR, van den Brink J, MacQuaide N et al (2018) Ryanodine receptor dispersion disrupts Ca2 release in failing cardiac myocytes. eLife 7

  • Landstrom AP, Kellen CA, Dixit SS et al (2011) Junctophilin-2 expression silencing causes cardiocyte hypertrophy and abnormal intracellular calcium-handling. Circ Heart Fail 4:214–223

    CAS  PubMed  PubMed Central  Google Scholar 

  • Laury-Kleintop LD, Mulgrew JR, Heletz I et al (2015) Cardiac-specific disruption of Bin1 in mice enables a model of stress- and age-associated dilated cardiomyopathy. J Cell Biochem 116:2541–2551

    CAS  PubMed  Google Scholar 

  • Lee E, Marcucci M, Daniell L et al (2002) Amphiphysin 2 (Bin1) and T-tubule biogenesis in muscle. Science 297:1193–1196

    CAS  PubMed  Google Scholar 

  • Liu C, Spinozzi S, Chen J-Y et al (2019) Nexilin is a new component of junctional membrane complexes required for cardiac T-tubule formation. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.119.039751

  • Liu G, Papa A, Katchman AN et al (2020) Mechanism of adrenergic CaV1.2 stimulation revealed by proximity proteomics. Nature 577:695–700

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lyon AR, MacLeod KT, Zhang Y et al (2009) Loss of T-tubules and other changes to surface topography in ventricular myocytes from failing human and rat heart. Proc Natl Acad Sci 106:6854–6859

    CAS  PubMed  Google Scholar 

  • Maio AD, Di Maio A, Karko K et al (2007) T-tubule formation in cardiac myocytes: two possible mechanisms? J Muscle Res Cell Motil 28:231–241

    PubMed  Google Scholar 

  • Marx SO, Gaburjakova J, Gaburjakova M et al (2001) Coupled gating between cardiac calcium release channels (ryanodine receptors). Circ Res 88:1151–1158

    CAS  PubMed  Google Scholar 

  • Mata ADL, De La Mata A, Tajada S et al (2019) BIN1 induces the formation of T-tubules and adult-like Ca2 release units in developing cardiomyocytes. Stem Cells 37:54–64

    Google Scholar 

  • Mazzarotto F, Tayal U, Buchan RJ et al (2020) Reevaluating the genetic contribution of monogenic dilated cardiomyopathy. Circulation 141:387–398

    CAS  PubMed  PubMed Central  Google Scholar 

  • McNutt NS (1975) Ultrastructure of the myocardial sarcolemma. Circ Res 37:1–13

    CAS  PubMed  Google Scholar 

  • Minamisawa S, Oshikawa J, Takeshima H et al (2004) Junctophilin type 2 is associated with caveolin-3 and is down-regulated in the hypertrophic and dilated cardiomyopathies. Biochem Biophys Res Commun 325:852–856

    CAS  PubMed  Google Scholar 

  • Mitchell RD, Simmerman HK, Jones LR (1988) Ca2+ binding effects on protein conformation and protein interactions of canine cardiac calsequestrin. J Biol Chem 263:1376–1381

    CAS  PubMed  Google Scholar 

  • Ohtsuka T, Nakanishi H, Ikeda W et al (1998) Nexilin: a novel actin filament-binding protein localized at cell-matrix adherens junction. J Cell Biol 143:1227–1238

    CAS  PubMed  PubMed Central  Google Scholar 

  • Parikh SS, Blackwell DJ, Gomez-Hurtado N et al (2017) Thyroid and glucocorticoid hormones promote functional T-tubule development in human-induced pluripotent stem cell-derived cardiomyocytes. Circ Res 121:1323–1330

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pásek M, Brette F, Nelson A et al (2008a) Quantification of t-tubule area and protein distribution in rat cardiac ventricular myocytes. Prog Biophys Mol Biol 96:244–257

    PubMed  Google Scholar 

  • Pásek M, Šimurda J, Orchard CH, Christé G (2008b) A model of the guinea-pig ventricular cardiac myocyte incorporating a transverse–axial tubular system. Prog Biophys Mol Biol 96:258–280

    PubMed  Google Scholar 

  • Piacentino V, Weber CR, Chen X et al (2003) Cellular basis of abnormal calcium transients of failing human ventricular myocytes. Circ Res 92:651–658

    CAS  PubMed  Google Scholar 

  • Prendiville TW, Guo H, Lin Z et al (2015) Novel roles of GATA4/6 in the postnatal heart identified through temporally controlled, cardiomyocyte-specific gene inactivation by adeno-associated virus delivery of Cre recombinase. PLoS One 10:e0128105

    PubMed  PubMed Central  Google Scholar 

  • Quick AP, Wang Q, Philippen LE et al (2017) SPEG (striated muscle preferentially expressed protein kinase) is essential for cardiac function by regulating junctional membrane complex activity. Circ Res 120:110–119

    CAS  PubMed  Google Scholar 

  • Razzaq A, Robinson IM, McMahon HT et al (2001) Amphiphysin is necessary for organization of the excitation-contraction coupling machinery of muscles, but not for synaptic vesicle endocytosis in Drosophila. Genes Dev 15:2967–2979

    CAS  PubMed  PubMed Central  Google Scholar 

  • Reynolds JO, Chiang DY, Wang W et al (2013) Junctophilin-2 is necessary for T-tubule maturation during mouse heart development. Cardiovasc Res 100:44–53

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rizzi N, Liu N, Napolitano C et al (2008) Unexpected structural and functional consequences of the R33Q homozygous mutation in cardiac calsequestrin: a complex arrhythmogenic cascade in a knock in mouse model. Circ Res 103:298–306

    CAS  PubMed  Google Scholar 

  • Ronaldson-Bouchard K, Ma SP, Yeager K et al (2018) Advanced maturation of human cardiac tissue grown from pluripotent stem cells. Nature. https://doi.org/10.1038/s41586-018-0016-3

  • Savio-Galimberti E, Frank J, Inoue M et al (2008) Novel features of the rabbit transverse tubular system revealed by quantitative analysis of three-dimensional reconstructions from confocal images. Biophys J 95:2053–2062

    CAS  PubMed  PubMed Central  Google Scholar 

  • Seidel T, Navankasattusas S, Ahmad A et al (2017) Sheet-like remodeling of the transverse tubular system in human heart failure impairs excitation-contraction coupling and functional recovery by mechanical unloading. Circulation 135:1632–1645

    PubMed  PubMed Central  Google Scholar 

  • Shang W, Lu F, Sun T et al (2014) Imaging Ca2+ Nanosparks in heart with a new targeted biosensor. Circ Res 114:412–420

  • Shiels HA, Galli GLJ (2014) The sarcoplasmic reticulum and the evolution of the vertebrate heart. Physiology 29:456–469

    CAS  PubMed  Google Scholar 

  • Shiferaw Y, Aistrup GL, Andrew Wasserstrom J (2012) Intracellular Ca2+ waves, afterdepolarizations, and triggered arrhythmias. Cardiovasc Res 95:265–268

  • Slupsky JR, Ohnishi M, Carpenter MR, Reithmeier RA (1987) Characterization of cardiac calsequestrin. Biochemistry 26:6539–6544

    CAS  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 84:266–275

    CAS  PubMed  Google Scholar 

  • Song L-S, Sobie EA, McCulle S et al (2006) Orphaned ryanodine receptors in the failing heart. Proc Natl Acad Sci 103:4305–4310

    CAS  PubMed  Google Scholar 

  • Sperelakis N, Rubio R (1971) An orderly lattice of axial tubules which interconnect adjacent transverse tubules in guinea-pig ventricular myocardium. J Mol Cell Cardiol 2:211–220

    CAS  PubMed  Google Scholar 

  • Stern MD (1992) Theory of excitation-contraction coupling in cardiac muscle. Biophys J 63:497–517

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stern MD, Song LS, Cheng H et al (1999) Local control models of cardiac excitation-contraction coupling. A possible role for allosteric interactions between ryanodine receptors. J Gen Physiol 113:469–489

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sumitomo N (2016) Current topics in catecholaminergic polymorphic ventricular tachycardia. J Arrhythm 32:344–351

    PubMed  Google Scholar 

  • Takeshima H (2002) Intracellular Ca2+ store in embryonic cardiac myocytes. Front Biosci 7:d1642–d1652

    CAS  PubMed  Google Scholar 

  • Takeshima H, Komazaki S, Nishi M et al (2000) Junctophilins: a novel family of junctional membrane complex proteins. Mol Cell 6:11–22

    CAS  PubMed  Google Scholar 

  • Trinkle-Mulcahy L (2019) Recent advances in proximity-based labeling methods for interactome mapping. F1000Res 8. https://doi.org/10.12688/f1000research.16903.1

  • Vangheluwe P, Louch WE, Ver Heyen M et al (2003) Ca2+ transport ATPase isoforms SERCA2a and SERCA2b are targeted to the same sites in the murine heart. Cell Calcium 34:457–464

    CAS  PubMed  Google Scholar 

  • Wagner E, Lauterbach MA, Kohl T et al (2012) Stimulated emission depletion live-cell super-resolution imaging shows proliferative remodeling of T-tubule membrane structures after myocardial infarction. Circ Res 111:402–414

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang SQ, Song LS, Lakatta EG, Cheng H (2001) Ca2+ signalling between single L-type Ca2+ channels and ryanodine receptors in heart cells. Nature 410:592–596

    CAS  PubMed  Google Scholar 

  • Wang S-Q, Song L-S, Xu L et al (2002) Thermodynamically irreversible gating of ryanodine receptors in situ revealed by stereotyped duration of release in Ca2 sparks. Biophys J 83:242–251

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang SQ, Stern MD, Rios E, Cheng H (2004) The quantal nature of Ca2+ sparks and in situ operation of the ryanodine receptor array in cardiac cells. Proc Natl Acad Sci 101:3979–3984

  • Wei S, Guo A, Chen B et al (2010a) T-Tubule remodeling during transition from hypertrophy to heart failure. Circ Res 107:520–531

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wei S, Guo A, Chen B et al (2010b) T-Tubule remodeling during transition from hypertrophy to heart failure. Circ Res 107:520–531

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wright PT, Nikolaev VO, O’Hara T et al (2014) Caveolin-3 regulates compartmentation of cardiomyocyte beta2-adrenergic receptor-mediated cAMP signaling. J Mol Cell Cardiol 67:38–48

    CAS  PubMed  Google Scholar 

  • Xu M, Wu H-D, Li R-C et al (2012) Mir-24 regulates junctophilin-2 expression in cardiomyocytes. Circ Res 111:837–841

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan Q, Fan G-C, Dong M et al (2007) Sarcoplasmic reticulum calcium overloading in junctin deficiency enhances cardiac contractility but increases ventricular automaticity. Circulation 115:300–309

    CAS  PubMed  Google Scholar 

  • Zhang L, Kelley J, Schmeisser G et al (1997) Complex formation between junctin, triadin, calsequestrin, and the ryanodine receptor. Proteins of the cardiac junctional sarcoplasmic reticulum membrane. J Biol Chem 272:23389–23397

    CAS  PubMed  Google Scholar 

  • Zhang H-B, Li R-C, Xu M et al (2013) Ultrastructural uncoupling between T-tubules and sarcoplasmic reticulum in human heart failure. Cardiovasc Res 98:269–276

    CAS  PubMed  Google Scholar 

  • Zhang C, Chen B, Guo A et al (2014) Microtubule-mediated defects in junctophilin-2 trafficking contribute to myocyte transverse-tubule remodeling and Ca2+ handling dysfunction in heart failure. Circulation 129:1742–1750

  • Zhang D, Li Y, Heims-Waldron DA et al (2017) Mitochondrial cardiomyopathy caused by elevated reactive oxygen species and impaired cardiomyocyte proliferation. Circ Res 122:7

    Google Scholar 

  • Ziman AP, Gómez-Viquez NL, Bloch RJ, Lederer WJ (2010) Excitation-contraction coupling changes during postnatal cardiac development. J Mol Cell Cardiol 48:379–386

    CAS  PubMed  Google Scholar 

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Acknowledgments

The authors thank Kamillmaksymilian Prondzynsk for critical comments on the manuscript.

Funding

FL was supported by a postdoctoral fellowship from the American Heart Association. WTP was supported by NIH grants R01 HL146634 and R21 HD094909.

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  1. Department of Cardiology, Boston Children’s Hospital, 300 Longwood Ave, Boston, MA, 02115, USA

    Fujian Lu & William T. Pu

  2. Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA, 02138, USA

    William T. Pu

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Lu, F., Pu, W.T. The architecture and function of cardiac dyads. Biophys Rev 12, 1007–1017 (2020). https://doi.org/10.1007/s12551-020-00729-x

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