The role of phospholamban and GSK3 in regulating rodent cardiac SERCA function

Cardiac contractile function is largely mediated by the regulation of Ca²⁺ cycling throughout the lifespan. The sarco(endo)plasmic reticulum Ca²⁺ ATPase (SERCA) pump is paramount to cardiac Ca²⁺ regulation, and it is well established that SERCA dysfunction pathologically contributes to cardiomyopathy and heart failure. Phospholamban (PLN) is a well-known inhibitor of the SERCA pump and its regulation of SERCA2a-the predominant cardiac SERCA isoform-contributes significantly to proper cardiac function. Glycogen synthase kinase 3 (GSK3) is a serine/threonine kinase involved in several metabolic pathways, and we and others have shown that it regulates SERCA function. In this mini-review, we highlight the underlying mechanisms behind GSK3's regulation of SERCA function specifically discussing changes in SERCA2a and PLN expression and its potential protection against oxidative stress. Ultimately, these recent findings that we discuss could have clinical implications in the treatment and prevention of cardiomyopathies and heart failure.