Although dilated cardiomyopathy (DCM) is known to result in cardiac contractile 
dysfunction, the underlying mechanisms are unclear. The sarcoplasmic reticulum 
(SR) is the main regulator of intracellular Ca2+ required for cardiac 
contraction and relaxation. We therefore hypothesized that abnormalities in both 
SR function and regulation will contribute to cardiac contractile dysfunction of 
the J2N-k cardiomyopathic hamster, an appropriate model of DCM. 
Echocardiographic assessment indicated contractile dysfunction, because the 
ejection fraction, fractional shortening, cardiac output, and heart rate were 
all significantly reduced in J2N-k hamsters compared with controls. Depressed 
cardiac function was associated with decreased cardiac SR Ca2+ uptake in the 
cardiomyopathic hamsters. Reduced SR Ca2+ uptake could be further linked to a 
decrease in the expression of the SR Ca(2+)-ATPase and cAMP-dependent protein 
kinase (PKA)-mediated phospholamban (PLB) phosphorylation at serine-16. 
Depressed PLB phosphorylation was paralleled with a reduction in the activity of 
SR-associated PKA, as well as an elevation in protein phosphatase activity in 
J2N-k hamster. The results of this study suggest that an alteration in SR 
function and its regulation contribute to cardiac contractile dysfunction in the 
J2N-k cardiomyopathic hamster.