Triadin 1 is a major transmembrane protein in cardiac junctional sarcoplasmic 
reticulum (SR), which forms a quaternary complex with the ryanodine receptor 
(Ca(2+) release channel), junctin, and calsequestrin. To better understand the 
role of triadin 1 in excitation-contraction coupling in the heart, we generated 
transgenic mice with targeted overexpression of triadin 1 to mouse atrium and 
ventricle, employing the alpha-myosin heavy chain promoter to drive protein 
expression. The protein was overexpressed 5-fold in mouse ventricles, and 
overexpression was accompanied by cardiac hypertrophy. The levels of two other 
junctional SR proteins, the ryanodine receptor and junctin, were reduced by 55% 
and 73%, respectively, in association with triadin 1 overexpression, whereas the 
levels of calsequestrin, the Ca(2+)-binding protein of junctional SR, and of 
phospholamban and SERCA2a, Ca(2+)-handling proteins of the free SR, were 
unchanged. Cardiac myocytes from triadin 1-overexpressing mice exhibited 
depressed contractility; Ca(2+) transients decayed at a slower rate, and cell 
shortening and relengthening were diminished. The extent of depression of cell 
shortening of triadin 1-overexpressing cardiomyocytes was rate-dependent, being 
more depressed under low stimulation frequencies (0.5 Hz), but reaching 
comparable levels at higher frequencies of stimulation (5 Hz). Spontaneously 
beating, isolated work-performing heart preparations overexpressing triadin 1 
also relaxed at a slower rate than control hearts, and failed to adapt to 
increased afterload appropriately. The fast time inactivation constant, tau(1), 
of the l-type Ca(2+) channel was prolonged in transgenic cardiomyocytes. Our 
results provide evidence for the coordinated regulation of junctional SR protein 
expression in heart independent of free SR protein expression, and furthermore 
suggest an important role for triadin 1 in regulating the contractile properties 
of the heart during excitation-contraction coupling.