Document Detail


Critical roles of junctophilin-2 in T-tubule and excitation-contraction coupling maturation during postnatal development.
MedLine Citation:
PMID:  23860812     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 (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.
CONCLUSION: Our data identify a critical role for JP2 in T-tubule and excitation-contraction coupling maturation during development.
Authors:
Biyi Chen; Ang Guo; Caimei Zhang; Rong Chen; Yanqi Zhu; Jiang Hong; William Kutschke; Kathy Zimmerman; Robert M Weiss; Leonid Zingman; Mark E Anderson; Xander H T Wehrens; Long-Sheng Song
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-07-16
Journal Detail:
Title:  Cardiovascular research     Volume:  100     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-09-23     Completed Date:  2014-06-16     Revised Date:  2014-10-09    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  54-62     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium / metabolism
Excitation Contraction Coupling / physiology*
Heart / growth & development*
Membrane Proteins / physiology*
Mice
Mice, Inbred C57BL
Myocytes, Cardiac / cytology*
Sarcolemma / physiology*
Grant Support
ID/Acronym/Agency:
HL091947/HL/NHLBI NIH HHS; HL113001/HL/NHLBI NIH HHS; HL62494/HL/NHLBI NIH HHS; HL70250/HL/NHLBI NIH HHS; NIH R01 HL089598/HL/NHLBI NIH HHS; NIH R01 HL090905/HL/NHLBI NIH HHS; NIH R01HL079031/HL/NHLBI NIH HHS; R01 HL070250/HL/NHLBI NIH HHS; R01 HL079031/HL/NHLBI NIH HHS; R01 HL090905/HL/NHLBI NIH HHS; R01 HL113001/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Membrane Proteins; 0/junctophilin; SY7Q814VUP/Calcium
Comments/Corrections

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