Abstract
The T-tubule (TT) system forms the structural basis for excitation-contraction coupling in heart and muscle cells. The morphogenesis of the TT system is a key step in the maturation of heart cells because it does not exist in neonatal cardiomyocytes. In the present study, we quantified the morphological changes in TTs during heart cell maturation and investigated the role of junctophilin-2 (JP2), a protein known to anchor the sarcoplasmic reticulum (SR) to TT, in changes to TT morphological parameters. Analysis of confocal images showed that the transverse elements of TTs increased, while longitudinal elements decreased during the maturation of TTs. Fourier transform analysis showed that the power of ∼2 μm spatial components increased with cardiomyocytes maturation. These changes were preceded by increased expression of JP2, and were reversed by JP2 knockdown. These findings indicate that JP2 is required for the morphogenesis of TTs during heart development.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Bers D M. Excitation-contraction Coupling and Cardiac Contractile Force. 2nd ed. Dordrecht (the Netherlands): Kluwer Academic Publisher, 2001
Forbes M S, Hawkey L A, Sperelakis N. The transverse-axial tubular system (TATS) of mouse myocardium: its morphology in the developing and adult animal. Am J Anat, 1984, 170: 143–162
Brette F, Orchard C. T-tubule function in mammalian cardiac myocytes. Circ Res, 2003, 92: 1182–1192
Soeller C, Cannell M B. Examination of the transverse tubular system in living cardiac rat myocytes by 2-photon microscopy and digital image-processing techniques. Circ Res, 1999, 84: 266–275
Cartwright E J, Oceandy D, Austin C, et al. Ca2+ signalling in cardiovascular disease: the role of the plasma membrane calcium pumps. Sci China Life Sci, 2011, 54: 691–698
Cheng H, Cannell M B, Lederer W J. Propagation of excitation-contraction coupling into ventricular myocytes. Pflugers Arch, 1994, 428: 415–417
Song L S, Guatimosim S, Gomez-Viquez L, et al. Calcium biology of the transverse tubules in heart. Ann New York Acad Sci, 2005, 1047: 99–111
Franzini-Armstrong C, Protasi F. Ryanodine receptors of striated muscles: a complex channel capable of multiple interactions. Physiol Rev, 1997, 77: 699–729
Franzini-Armstrong C, Protasi F, Ramesh V. Shape, size, and distribution of Ca(2+) release units and couplons in skeletal and cardiac muscles. Biophys J, 1999, 77: 1528–1539
Kimlicka L, Van Petegem F. The structural biology of ryanodine receptors. Sci China Life Sci, 2011, 54: 712–724
Lopez-Lopez J R, Shacklock P S, Balke C W, et al. Local calcium transients triggered by single L-type calcium channel currents in cardiac cells. Science, 1995, 268: 1042–1045
Berridge M J, Bootman M D, Roderick H L. Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev, 2003, 4: 517–529
Bers D M. Cardiac excitation-contraction coupling. Nature, 2002, 415: 198–205
Di Maio A, Karko K, Snopko R M, et al. T-tubule formation in cardiomyocytes: two possible mechanisms? J Muscle Res Cell Motil, 2007, 28: 231–241
Takeshima H, Komazaki S, Nishi M, et al. Junctophilins: a novel family of junctional membrane complex proteins. Mol Cell, 2000, 6: 11–22
Escobar A L, Ribeiro-Costa R, Villalba-Galea C, et al. Developmental changes of intracellular Ca2+ transients in beating rat hearts. Am J Physiol, 2004, 286: H971–H978
Snopko R M, Ramos-Franco J, Di Maio A, et al. Ca2+ sparks and cellular distribution of ryanodine receptors in developing cardiomyocytes from rat. J Mol Cell Cardiol, 2008, 44: 1032–1044
Nishi M, Mizushima A, Nakagawara K, et al. Characterization of human junctophilin subtype genes. Biochem Biophys Res Commun, 2000, 273: 920–927
Garbino A, Wehrens X H. Emerging role of junctophilin-2 as a regulator of calcium handling in the heart. Acta Pharmacol Sin, 2010, 31: 1019–1021
Hirata Y, Brotto M, Weisleder N, et al. Uncoupling store-operated Ca2+ entry and altered Ca2+ release from sarcoplasmic reticulum through silencing of junctophilin genes. Biophys J, 2006, 90: 4418–4427
Landstrom A P, Kellen C A, Dixit S S, et al. Junctophilin-2 expression silencing causes cardiocyte hypertrophy and abnormal intracellular calcium-handling. Circulation, 2011, 4: 214–223
van Oort R J, Garbino A, Wang W, et al. Disrupted junctional membrane complexes and hyperactive ryanodine receptors after acute junctophilin knockdown in mice. Circulation, 2011, 123: 979–988
Wei S, Guo A, Chen B, et al. T-tubule remodeling during transition from hypertrophy to heart failure. Circ Res, 2010, 107: 520–531
Wu H D, Xu M, Li R C, et al. Ultrastructural remodelling of Ca(2+) signalling apparatus in failing heart cells. Cardiovas Res, 2012, 95: 430–438
Fu Y, Zhang G Q, Hao X M, et al. Temperature dependence and thermodynamic properties of Ca2+ sparks in rat cardiomyocytes. Biophys J, 2005, 89: 2533–2541
Song L S, Sobie E A, McCulle S, et al. Orphaned ryanodine receptors in the failing heart. Proc Natl Acad Sci USA, 2006, 103: 4305–4310
Liang X, Mei Y, Huang X, et al. Junctophilin 2 knockdown interfere with mitochondrium status in ESC-CMs and cardiogenesis of ES cells. J Cell Biochem, 2012, 113: 2884–2894
Perez C G, Copello J A, Li Y, et al. Ryanodine receptor function in newborn rat heart. Am J Physiol, 2005, 288: H2527–H2540
Author information
Authors and Affiliations
Corresponding author
Additional information
This article is published with open access at Springerlink.com
Rights and permissions
Open Access This article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
About this article
Cite this article
Han, J., Wu, H., Wang, Q. et al. Morphogenesis of T-tubules in heart cells: the role of junctophilin-2. Sci. China Life Sci. 56, 647–652 (2013). https://doi.org/10.1007/s11427-013-4490-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-013-4490-4