Critical roles of junctophilin-2 in T-tubule and excitation-contraction coupling maturation during postnatal development

Cardiovasc Res. 2013 Oct 1;100(1):54-62. doi: 10.1093/cvr/cvt180. Epub 2013 Jul 16.


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.

Keywords: Calcium; Excitation–contraction coupling; Heart development; Junctophilin-2; T-tubules.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Excitation Contraction Coupling / physiology*
  • Heart / growth & development*
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Myocytes, Cardiac / cytology*
  • Sarcolemma / physiology*


  • Membrane Proteins
  • junctophilin
  • Calcium