Journal article
Critical roles of junctophilin-2 in T-tubule and excitation-contraction coupling maturation during postnatal development
Cardiovascular research, Vol.100(1), pp.54-62
10/01/2013
DOI: 10.1093/cvr/cvt180
PMCID: PMC3778961
PMID: 23860812
Abstract
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.
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 (TT(power)) index revealed a progressive increase in TT(power) between postnatal Days 10 and 19. By postnatal Day 19, TT(power) 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 TT(power). 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 Ca(2+) transient amplitude and marked increase in Ca(2+) release dyssynchrony, Ca(2+) alternans, and spontaneous Ca(2+) waves, leading to contractile failure.
Our data identify a critical role for JP2 in T-tubule and excitation-contraction coupling maturation during development.
Details
- Title: Subtitle
- Critical roles of junctophilin-2 in T-tubule and excitation-contraction coupling maturation during postnatal development
- Creators
- Biyi Chen - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver, College of Medicine, Iowa City, IA 52242, USAAng GuoCaimei ZhangRong ChenYanqi ZhuJiang HongWilliam KutschkeKathy ZimmermanRobert M WeissLeonid ZingmanMark E AndersonXander H T WehrensLong-Sheng Song
- Resource Type
- Journal article
- Publication Details
- Cardiovascular research, Vol.100(1), pp.54-62
- DOI
- 10.1093/cvr/cvt180
- PMID
- 23860812
- PMCID
- PMC3778961
- ISSN
- 0008-6363
- eISSN
- 1755-3245
- Grant note
- R01 HL113001 / NHLBI NIH HHS HL70250 / NHLBI NIH HHS R01 HL079031 / NHLBI NIH HHS R01 HL070250 / NHLBI NIH HHS HL62494 / NHLBI NIH HHS R01 HL090905 / NHLBI NIH HHS HL091947 / NHLBI NIH HHS HL113001 / NHLBI NIH HHS NIH R01 HL090905 / NHLBI NIH HHS NIH R01HL079031 / NHLBI NIH HHS NIH R01 HL089598 / NHLBI NIH HHS
- Language
- English
- Date published
- 10/01/2013
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984094658702771
Metrics
26 Record Views