Triadin is involved in the regulation of cardiac excitation-contraction 
coupling. However, the extent of its contribution to the regulation of 
sarcoplasmic reticulum (SR) Ca release remains unclear, because overexpression 
of triadin in single-transgenic mice was associated with the downregulation of 
its homologous protein, junctin. In the present study, this problem was 
circumvented by cross-breeding of mice with heart-directed overexpression of 
triadin and junctin (JxT). This resulted in a stable approximately threefold 
expression of total triadin but unchanged junctin protein. Transgenic mice 
exhibited cardiac hypertrophy and structural abnormalities of myofibrils. 
Measurement of cardiac function by echocardiography and edge detection in 
myocytes revealed an impaired relaxation in JxT mice. The stimulation of 
beta-adrenergic receptors resulted in a depressed contractility and an impaired 
relaxation in catheterized hearts and myocytes of JxT mice. The use of a maximum 
stimulation frequency (5 Hz) was associated with both a lower shortening and 
relengthening in isolated myocytes of JxT mice. The contractile effects in JxT 
myocytes were paralleled by similar changes of the intracellular Ca 
concentration ([Ca](i)) peak amplitude and Ca transient decay kinetics at basal 
conditions, under administration of isoproterenol, and with high-frequency 
stimulation. Finally, we found a higher caffeine-induced [Ca](i) peak amplitude 
in JxT myocytes. Our data show that the stable expression of triadin, 
independent of junctin expression, resulted in cardiac hypertrophy, prolonged 
basal relaxation, a depressed response to beta-adrenergic agonists, and altered 
Ca transients. Thus the maintenance of triadin expression is essential for 
normal SR Ca cycling and contractile function.