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 R Jones

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)


OBJECTIVE: Junctin is a major transmembrane protein in cardiac junctional sarcoplasmic reticulum, which forms a quaternary complex with the ryanodine receptor (Ca(2+) 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 alpha-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: Ca(2+) 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 Ca(2+) transients was lower in cardiomyocytes from junctin-overexpressing mice. The inactivation kinetics of L-type Ca(2+) channel were prolonged in junctin-overexpressing cardiomyocytes using Ca(2+) or Ba(2+) as charge carriers.

CONCLUSION: Our data provide evidence that cardiac-specific overexpression of junctin is accompanied by impaired myocardial relaxation with prolonged Ca(2+) transient kinetics on the cardiomyocyte level.

Original languageEnglish
Pages (from-to)369-79
Number of pages11
JournalCardiovascular Research
Issue number2
Publication statusPublished - 1 Aug 2003


  • Animals
  • Calcium
  • Calcium Channels, L-Type
  • Calcium-Binding Proteins
  • Cardiomegaly
  • Carrier Proteins
  • Cell Size
  • Echocardiography, Doppler
  • Electric Stimulation
  • Membrane Proteins
  • Mice
  • Mice, Transgenic
  • Mixed Function Oxygenases
  • Muscle Proteins
  • Muscle Relaxation
  • Myocardial Contraction
  • Myocytes, Cardiac
  • Papillary Muscles
  • Ryanodine Receptor Calcium Release Channel


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