Junctin is a transmembrane protein of the cardiac junctional sarcoplasmic 
reticulum (SR) that binds to the ryanodine receptor, calsequestrin, and triadin 
1. This quaternary protein complex is thought to facilitate SR Ca2+ release. To 
improve our understanding of the contribution of junctin to the regulation of SR 
function, we examined the age-dependent effects of junctin overexpression in the 
atrium of 3-, 6-, and 18-wk-old transgenic mice. The ratio of atrial weight and 
body weight was unchanged between junctin-overexpressing (JCN) and wild-type 
(WT) mice at all ages investigated (n=6-8). The protein expression of triadin 1 
was decreased starting in 3-wk-old JCN atria (by 69%), whereas the expression of 
the ryanodine receptor was diminished in 6- (by 48%) and 18-wk-old (by 57%) JCN 
atria compared with age-matched WT atria. Force of contraction was decreased by 
35% in 18-wk-old JCN compared with age-matched WT left atrial muscle strips, 
which was accompanied by a prolonged time of relaxation (48.1 +/- 0.9 vs. 44.2 
+/- 0.8 ms, respectively, n=6-8, P <0.05). The spontaneous beating rate of 
isolated right atria was higher in 18-wk-old JCN mice compared with age-matched 
WT mice (389 +/- 10 vs. 357 +/- 6 beats/min, respectively, n=6-8, P <0.05). 
Heart rate was lower by 9% in telemetric ECG recordings in 18-wk-old JCN mice 
during stress tests. Three-week-old JCN atria exhibited a higher potentiation of 
force of contraction at rest pauses of 30 s (by 13%) and of 300 s (by 35%), 
suggesting increased SR Ca2+ content. This was consistent with the higher force 
of contraction in 3-wk-old JCN atria (by 29%) compared with age-matched WT atria 
(by 10%) under the administration of caffeine. We conclude that in 3-wk-old 
atria, junctin overexpression was associated with a reduced expression of 
triadin 1 resulting in a higher SR Ca2+ load without changes in contractility or 
heart rate. In 6-wk-old JCN atria, the compensatory downregulation of the 
ryanodine receptor may offset the effects of junctin overexpression. Finally, 
the progressive decrease in ryanodine receptor density may contribute to the 
decreased atrial contractility and lower heart rate during stress in 18-wk-old 
JCN mice.