Temporal Sensitivity of Protein Kinase A Activation in Late-Phase Long Term Potentiation
Figure 2
Temporal sensitivity of PKA and CaMKII activation during L-LTP induction.
(A) Activation of PKA by different temporal patterns of stimulation. A1 shows 1400 sec of simulation time and A2 shows the first 200 sec to better show the four trains of massed stimulation. Though the peak is 1.4 times greater for massed trains, the cumulative activity of PKA activity is ∼60% greater for spaced trains (2321 nM-sec versus 1455 nM-sec). (B) The increase in phosphoCaMKII activity (sum of Ca4-calmodulin trapped and autonomous forms) is smaller for spaced than massed stimulations. The positive feedback loop is visible in the spaced case, in which increments of phosphorylated CaMKII increase with subsequent trains. (C) Cumulative PKA activity (measured as area under the curve) shows an exponential increase (τ = 8.5 sec) as inter-train interval is increased. The peak phosphoCaMKII decreases exponentially with temporal interval, exhibiting a frequency sensitivity opposite to that of PKA. The time constant of the decrease, τ, is 20.8 sec. The sum of the normalized kinase activity (divided by two for graphical purposes) is constant for inter-train intervals greater than 3 sec, suggesting that the increase in PKA is compensating for a phosphoCaMKII deficit with larger for inter-train intervals.