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.