抄録
A growing body of evidence, including studies from genetically engineered mouse models and human patients, has shown that Ca2+ cycling and Ca2+-dependent signaling pathways via sarcoplasmic reticulum (SR) play an important role in normal cardiac function as well as heart diseases. Among SR proteins, cardiac SR Ca2+ ATPase (SERCA2a) plays a pivotal role in regulating the rate of Ca2+ re-uptake during relaxation in the heart. The activity of SERCA2a is mainly regulated by its endogenous inhibitor, phospholamban (PLN). We have demonstrated that the regulation of SERCA2a activity via PLN may cause human cardiomyopathy and the inhibition of interaction between SERCA2a and PLN may have potential therapeutic value for heart diseases such as cardiomyopathy and heart failure. In addition to PLN, newly identified SR proteins such as sarcolipin and sarcalumenin also regulate Ca2+ re-uptake during relaxation through the interaction with SERCA2a. Sarcolipin is restrictedly expressed in the atria and its expression is down-regulated in the loaded atria. Sarcalumenin is a Ca2+ binding glycoprotein located in the lumen of the SR and thought to regulate Ca2+ transport and storage in the SR. Both heart-specific sarcolipin transgenic mice and sarcalumenin knockout mice exhibit relaxation-dominant cardiac dysfunction. The physiological role of sarcolipin and sarcalumenin will be further discussed. [Jpn J Physiol 55 Suppl:S55 (2005)]
