OBJECTIVE: Ca2+ release from the cardiac junctional sarcoplasmic reticulum (SR) 
is regulated by a complex of proteins, including the ryanodine receptor (RyR), 
calsequestrin (CSQ), junctin (JCN), and triadin 1 (TRD). Moreover, triadin 1 
appears to anchor calsequestrin to the ryanodine receptor.
METHODS: To determine whether triadin 1 overexpression alters 
excitation-contraction coupling, we examined the effects of cardiac-specific 
overexpression of triadin 1 on SR Ca2+ handling and contractility in transgenic 
(TG) compared to wild-type (WT) mice.
RESULTS: The overexpression of triadin 1 was associated with an enhanced SR Ca2+ 
load, reflected by a 22% higher amplitude of caffeine-induced Ca2+ transients. 
The decline of Ca2+ transients during caffeine exposure was prolonged by 57%. 
The detection of resting spontaneous SR Ca2+ release events (Ca2+ sparks) 
revealed an increased amplitude (by 16%), decline (by 47%), and width (by 47%) 
in TG. This was associated with a redistribution of Ca2+ spark amplitudes from 
one population to two populations. Measurement of cardiac function by 
echocardiography and left ventricular (LV) catheterization revealed a decreased 
cardiac contractility in vivo. The impaired response to beta-adrenergic receptor 
(beta-AR) stimulation in TG hearts was associated with an increased protein 
expression of beta-AR kinase 1. In addition, the increase of the L-type Ca2+ 
peak current and the increase of phospholamban (PLB) phosphorylation at Thr17 
were reduced under beta-AR stimulation.
CONCLUSION: Taken together, our data suggest that triadin 1 overexpression 
results in a complex modulation of SR Ca2+ handling, which may contribute, at 
least in part, to the depressed basal contractility and the blunted response to 
beta-adrenergic agonists in TG mice.