We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Critical roles of junctophilin-2 in T-tubule and excitation–contraction coupling maturation during postnatal development.
- Authors
Chen, Biyi; Guo, Ang; Zhang, Caimei; Chen, Rong; Zhu, Yanqi; Hong, Jiang; Kutschke, William; Zimmerman, Kathy; Weiss, Robert M.; Zingman, Leonid; Anderson, Mark E.; Wehrens, Xander H.T.; Song, Long-Sheng
- Abstract
Aims Emerging evidence indicates a critical role for junctophilin-2 (JP2) in T-tubule integrity and assembly of cardiac dyads in adult ventricular myocytes. In the postnatal stage, one of the critical features of myocyte maturation is development of the T-tubule system, though the mechanisms remain poorly understood. In this study, we aim to determine whether JP2 is required for normal cardiac T-tubule maturation. Methods and results Using in situ confocal imaging of intact murine hearts, we found T-tubules were absent in both left- and right-ventricular myocytes at postnatal Day 8 and did not appear until Day 10. Quantification of T-tubule structural integrity using the T-tubule power (TTpower) index revealed a progressive increase in TTpower between postnatal Days 10 and 19. By postnatal Day 19, TTpower was similar to that in adult murine cardiomyocytes, indicative of a nearly matured T-tubule network. JP2 levels increased dramatically during development, reaching levels observed in adult hearts by postnatal Day 14. Deficiency of JP2, using a mouse model in which a JP2-specific shRNA is expressed during embryonic development, severely impaired T-tubule maturation, with equivalent decreases in the left- and right-ventricular TTpower. We also detected a gradual increase in the density of transverse but not longitudinal tubules during development, and JP2 deficiency abolished the increase in the density of transverse elements. Alterations in T-tubules caused significant reduction in Ca2+ transient amplitude and marked increase in Ca2+ release dyssynchrony, Ca2+ alternans, and spontaneous Ca2+ waves, leading to contractile failure. Conclusion Our data identify a critical role for JP2 in T-tubule and excitation–contraction coupling maturation during development.
- Subjects
HEART ventricles; MUSCLE cells; MYOCARDIUM; LABORATORY mice; HEART cells; HEART development; GENE expression
- Publication
Cardiovascular Research, 2013, Vol 100, Issue 1, p54
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1093/cvr/cvt180