Fig. 6.

PKA compartmentation drives differential activation of PKA substrates associated with contractility and hypertrophy. A, Model prediction for phosphorylated PLB and CREB sensitivity to ISO. p-PLB and p-CREB EC₅₀s parallel cytosolic and nuclear PKA EC₅₀s, respectively. B, Western blot analysis indicates PLB phosphorylation is significantly more sensitive to ISO than CREB phosphorylation (n = 3 experiments each). C, Representative Ca²⁺ transient measurements from control and 1 μmol/L ISO-stimulated myocytes paced at 1 Hz. D, Representative automated cell segmentations from myocytes cultured in 1 μmol/L ISO for 24 hours. E, ISO-stimulated Ca²⁺ enhancements exhibit high ISO sensitivity (n ≥ 3 experiments per ISO concentration), while 24 hour myocyte hypertrophy responses are less sensitive to ISO (n > 250 cells per ISO concentration).