CaMKII effects on inotropic but not lusitropic force frequency responses require phospholamban

► Force-frequency relation (FFR) was blunted in CaMKII inhibition (AC3-I) hearts. ► Similar negative FFR was found in PLN−/− and PLN−/− x AC3-I mouse hearts. ► CaMKII phosphorylated myofilament proteins but did not affect calcium sensitivity. ► PLN deletion eliminated FDAR and CaMKII inhibition further impaired relaxation. ► PLN is critical for CaMKII effects on FFR.