SERCA2a activity correlates with the force-frequency relationship in human myocardium

Area of Science:

• Cardiology
• Molecular Biology
• Biochemistry

Background:

• Sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a) and phospholamban (PLB) are critical regulators of cardiac contractility.
• Dysfunction in SERCA2a and PLB is implicated in heart failure, but their precise relationship in human failing myocardium remains unclear.

Purpose of the Study:

• To investigate the correlation between protein expression and function of SERCA2a and PLB in nonfailing and failing human myocardium.
• To determine the relationship between SERCA2a/PLB and the force-frequency relationship (FFR) in human cardiac chambers.

Main Methods:

• Analysis of SERCA2a activity and protein expression, and PLB phosphorylation in right atrium (RA) and left ventricle (LV) of nonfailing (NF) and dilated cardiomyopathy (DCM) hearts.
• Measurement of the force-frequency relationship (FFR) in human myocardial samples.

Main Results:

• SERCA2a activity was significantly decreased in the LV of DCM hearts, while protein expression remained unchanged across groups and chambers.
• PLB phosphorylation was higher in the LV compared to the RA in both NF and DCM hearts.
• SERCA2a function, not protein expression, showed a strong correlation with FFR parameters in both NF and DCM human hearts.

Conclusions:

• SERCA2a function, modulated by PLB phosphorylation at Ser(16) and Thr(17), is a key determinant of cardiac contractility in human hearts.
• While PLB phosphorylation is crucial, an unknown mechanism may also directly influence SERCA2a regulation in cardiac function.