The effective calcium/calmodulin concentration determines the sensitivity of CaMKII to the frequency of calcium oscillations

Calcium/calmodulin-dependent protein kinase II (CaMKII) is involved in the induction of many forms of synaptic plasticity in the brain. Experimental and computational studies have shown that CaMKII is sensitive to the frequency of oscillatory Ca signals. Here we demonstrate that in a simple, commonly used kinetic model of CaMKII phosphorylation, the overall phosphorylation rate under sustained application of Ca ∈- ∈CaM pulses ultimately depends on the average ('effective') concentration of Ca ∈-∈CaM in the system, rather than on the pulse frequency itself. As a corollary, equal phosphorylation levels are achieved in response to pulsed and constant applications of equal effective concentrations of Ca ∈-∈CaM.