Temporal Sensitivity of Protein Kinase A Activation in Late-Phase Long Term Potentiation
Figure 6
The increase in PKA activity due to spaced stimulation propagates to downstream targets inhibitor-1 and protein phosphatase 1.
(A) The amount of phosphorylated inhibitor-1 is ∼50% higher for spaced than massed stimulation. The initial decrease in phosphorylated inhibitor-1 (below baseline) is due to activation of protein phosphatase 2B. (B) The sharp peaks of protein phosphatase 1 during stimulation are caused by the initial decrease of phosphorylated inhibitor-1. These transient increases are followed by longer periods of decrease in free protein phosphatase 1 below basal level, caused by an increase of phosphorylated inhibitor-1. This simulation shows the concentration of protein phosphatase 1 is reduced ∼50% more by the spaced stimulation protocol than the massed protocol (in the legend a negative value of area under the curve denotes a decrease in activity).