SERCA2a activity correlates with the force-frequency relationship in humanmyocardium

The present investigation addresses whether protein expression and function of sarco( endo) plasmic reticulum Ca2+-ATPase (SERCA2a) and phospholamban (PLB) correlate in failing and nonfailing human myocardium. SERCA2a activit y and protein expression, PLB phosphorylation, and the force-frequency rela tionship (FFR) have been determined in right atrium (RA) and left ventricle (LV) from nonfailing (NF, n = 12) and terminally failing [dilated cardiomy opathy (DCM), n = 12] human hearts. Only in LV of DCM hearts was SERCA2a ac tivity significantly decreased [maximal turnover rate (V-max) = 196 +/- 11 and 396 +/- 30 nmol . mg(-1) . min(-1) in LV and RA, respectively], whereas protein expression of SERCA2a in the different chambers was unchanged in N F (3.9 +/- 0.3 and 3.2 +/- 0.4 densitometric units in LV and RA, respective ly) and DCM hearts (4.8 +/- 0.8 and 3.4 +/- 0.1 densitometric units in LV a nd RA, respectively). Phosphorylation of PLB was higher in LV than in RA in NF (Ser(16) : 180.5 +/- 19.0 vs. 56.8 +/- 6.0 densitometric units; Thr(17) : 174.6 +/- 11.2 vs. 37.4 +/- 8.9 densitometric units) and DCM hearts (Ser (16) : 132.0 +/- 5.4 vs. 22.4 +/- 3.5 densitometric units; Thr(17) : 131.2 +/- 10.9 vs. 9.2 +/- 2.4 densitometric units). SERCA2a function, but not pr otein expression, correlated well with the functional parameters of the FFR in DCM and NF human hearts. Regulation of SERCA2a function depends on the phosphorylation of PLB at Ser(16) and Thr(17). However, direct SERCA2a regu lation might also be affected by an unknown mechanism.