Increased contractility and altered Ca2+ transients of mouse heart myocytes conditionally expressing PKC beta

Activation of protein kinase C (PKC) in heart muscle signals hypertrophy an d may also directly affect contractile function. We tested this idea using a transgenic (TG) mouse model in which conditionally expressed PKC beta was turned on at 10 wk of age and remained on for either 6 or 10 mo. Compared with controls, TG cardiac myocytes demonstrated an increase in the peak amp litude of the Ca2+ transient, an increase in the extent and rate of shorten ing, and an increase in the rate of relengthening at both 6 and 10 mo of ag e. Phospholamban phosphorylation and Ca2+-uptake rates of sarcoplasmic reti culum vesicles were the same in TG and control heart preparations. At 10 mo , TG skinned fiber bundles demonstrated the same sensitivity to Ca2+ as con trols, but maximum tension was depressed and there was increased myofilamen t protein phosphorylation. Our results differ from studies in which PKC bet a was constitutively overexpressed in the heart and in studies that reporte d a depression of myocyte contraction with no change in the Ca2+ transient.