ORAL PRESENTATION Open Access Does CaMKII decode Ca2+ oscillations?

Ca2+/calmodulin-dependent protein kinase II (CaMKII), which is present in high concentrations in the brain, contributes to many forms of synaptic plasticity. The induction of synaptic plasticity by CaMKII involves an intracellular signalling cascade that links neuronal Ca2+ signals with the phosphorylation of neurotransmitter receptors; an important step in this biochemical cascade is the autophosphorylation of CaMKII after binding of Ca2+/calmodulin (Ca4-CaM). The dependence of this autophosphorylation reaction on the temporal structure of Ca4-CaM signals has been investigated in previous experiments [1] and computer simulations [2]. These experimental and theoretical stu-dies have indicated that the autophosphorylation of CaMKII is sensitive to the frequency of repetitive Ca2+ pulses, and it has been concluded that CaMKII can decode oscillatory Ca2+ signals [1,2]. Here, we apply a simplified version of the commonly used CaMKII activation model by Dupont and colla-borators [2] to investigate the mechanism that underlies the dependence of the overall autophosphorylation kinetics on the frequency of Ca2+ oscillations. In the simulations by Dupont et al., CaMKII was subjected to different average, or ‘effective’, Ca4-CaM concentrations, which in turn affected the average concentration of the CaMKII subunits, and the autophosphorylation kinetics. We first replicate the simulation results presented in [2] with our simplified model (Figure 1A). To identify the mechanism that underlies the observed frequency dependence, we then rescale the Ca4-CaM concentra-tions to an equal effective concentration, and compare the phosphorylation kinetics (Figure 1B). We demon-strate that in our model the overall phosphorylation rate under sustained application of Ca4-CaM pulses depend