Impaired relaxation in transgenic mice overexpressing junctin

Uwe Kirchhefer, Joachim Neumann, Donald M. Bers, Igor B. Buchwalow, Larissa Fabritz, Gabriela Hanske, Isabel Justus, Burkhard Riemann, Wilhelm Schmitz, Larry Jones

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Objective: Junctin is a major transmembrane protein in cardiac junctional sarcoplasmic reticulum, which forms a quaternary complex with the ryanodine receptor (Ca2+ release channel), triadin, and calsequestrin. Methods: To better understand the role of junctin in excitation-contraction coupling in the heart, we generated transgenic mice with targeted overexpression of junctin to mouse heart, using the α-MHC promoter to drive protein expression. Results: The protein was overexpressed 10-fold in mouse ventricles and overexpression was accompanied by cardiac hypertrophy (19%). The levels of two other junctional SR-proteins, the ryanodine receptor and triadin, were reduced by 32% and 23%, respectively. However, [3H]ryanodine binding and the expression levels of calsequestrin, phospholamban and SERCA2a remained unchanged. Cardiomyocytes from junctin-overexpressing mice exhibited impaired relaxation: Ca2+ transients decayed at a slower rate and cell relengthening was prolonged. Isolated electrically stimulated papillary muscles from junctin-overexpressing hearts exhibited prolonged mechanical relaxation, and echocardiographic parameters of relaxation were prolonged in the living transgenic mice. The amplitude of caffeine-induced Ca2+ transients was lower in cardiomyocytes from junctin-overexpressing mice. The inactivation kinetics of L-type Ca2+ channel were prolonged in junctin-overexpressing cardiomyocytes using Ca2+ or Ba2+ as charge carriers. Conclusion: Our data provide evidence that cardiac-specific overexpression of junctin is accompanied by impaired myocardial relaxation with prolonged Ca2+ transient kinetics on the cardiomyocyte level.

Original languageEnglish
Pages (from-to)369-379
Number of pages11
JournalCardiovascular Research
Volume59
Issue number2
DOIs
StatePublished - Aug 1 2003

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Cardiac Myocytes
Transgenic Mice
Calsequestrin
Ryanodine Receptor Calcium Release Channel
Proteins
Excitation Contraction Coupling
Ryanodine
Papillary Muscles
Cardiomegaly
Sarcoplasmic Reticulum
Caffeine
triadin

Keywords

  • Calcium (cellular)
  • Contractile function
  • E-contraction coupling
  • Hypertrophy
  • SR (function)

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Kirchhefer, U., Neumann, J., Bers, D. M., Buchwalow, I. B., Fabritz, L., Hanske, G., ... Jones, L. (2003). Impaired relaxation in transgenic mice overexpressing junctin. Cardiovascular Research, 59(2), 369-379. https://doi.org/10.1016/S0008-6363(03)00432-2

Impaired relaxation in transgenic mice overexpressing junctin. / Kirchhefer, Uwe; Neumann, Joachim; Bers, Donald M.; Buchwalow, Igor B.; Fabritz, Larissa; Hanske, Gabriela; Justus, Isabel; Riemann, Burkhard; Schmitz, Wilhelm; Jones, Larry.

In: Cardiovascular Research, Vol. 59, No. 2, 01.08.2003, p. 369-379.

Research output: Contribution to journalArticle

Kirchhefer, U, Neumann, J, Bers, DM, Buchwalow, IB, Fabritz, L, Hanske, G, Justus, I, Riemann, B, Schmitz, W & Jones, L 2003, 'Impaired relaxation in transgenic mice overexpressing junctin', Cardiovascular Research, vol. 59, no. 2, pp. 369-379. https://doi.org/10.1016/S0008-6363(03)00432-2
Kirchhefer U, Neumann J, Bers DM, Buchwalow IB, Fabritz L, Hanske G et al. Impaired relaxation in transgenic mice overexpressing junctin. Cardiovascular Research. 2003 Aug 1;59(2):369-379. https://doi.org/10.1016/S0008-6363(03)00432-2
Kirchhefer, Uwe ; Neumann, Joachim ; Bers, Donald M. ; Buchwalow, Igor B. ; Fabritz, Larissa ; Hanske, Gabriela ; Justus, Isabel ; Riemann, Burkhard ; Schmitz, Wilhelm ; Jones, Larry. / Impaired relaxation in transgenic mice overexpressing junctin. In: Cardiovascular Research. 2003 ; Vol. 59, No. 2. pp. 369-379.
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