Energy metabolism and Ca(2+) handling serve critical roles in cardiac physiology 
and pathophysiology. Peroxisome proliferator-activated receptor gamma 
coactivator 1 alpha (PGC-1 alpha) is a multi-functional coactivator that is 
involved in the regulation of cardiac mitochondrial functional capacity and 
cellular energy metabolism. However, the regulation of PGC-1 alpha in cardiac 
Ca(2+) signaling has not been fully elucidated. To address this issue, we 
combined confocal line-scan imaging with off-line imaging processing to 
characterize calcium signaling in cultured adult rat ventricular myocytes 
expressing PGC-1 alpha via adenoviral transduction. Our data shows that 
overexpressing PGC-1 alpha improved myocyte contractility without increasing the 
amplitude of Ca(2+) transients, suggesting that myofilament sensitivity to 
Ca(2+) increased. Interestingly, the decay kinetics of global Ca(2+) transients 
and Ca(2+) waves accelerated in PGC-1 alpha-expressing cells, but the decay rate 
of caffeine-elicited Ca(2+) transients showed no significant change. This 
suggests that sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a), but not 
Na(+)/Ca(2+) exchange (NCX) contribute to PGC-1 alpha-induced cytosolic Ca(2+) 
clearance. Furthermore, PGC-1 alpha induced the expression of SERCA2a in 
cultured cardiac myocytes. Importantly, overexpressing PGC-1 alpha did not 
disturb cardiac Ca(2+) homeostasis, because SR Ca(2+) load and the propensity 
for Ca(2+) waves remained unchanged. These data suggest that PGC-1 alpha can 
ameliorate cardiac Ca(2+) cycling and improve cardiac work output in response to 
physiological stress. Unraveling the PGC-1 alpha-calcium handling pathway sheds 
new light on the role of PGC-1 alpha in the therapy of cardiac diseases.