Phospholamban phosphorylation and SERCA 2a function in human heart failure

Reduced phosphorylation of phospholamban might account for increased inhibition of SERCA 2a activity in failing human myocardium. Reduced Ca2- sensitivity of SERCA 2a was found in myocardium from failing human hearts, PKA stimulation restored Ca2+ sensitivity of SERCA 2a lo levels of the NF controls. Reduced V-max of SERCA 2a activity was also determined in DCM. CaM kinase (CamK) increased V-max of SERCA 2a to control levels. in conclusion, the reduced Ca2+ sensitivity and V-max of SERCA Za in failing human myocardium could at least partly be explained by reduced endogenous PKA and CamK activity with increased inhibitory control of phospholamban on SERCA 2 activity ii, failing human myocardium.