Does CaMKII decode Ca2+oscillations?
© Pinto et al; licensee BioMed Central Ltd. 2012
Published: 16 July 2012
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  and computer simulations . These experimental and theoretical studies 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 collaborators  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.
Our simulation results indicate that the notion of CaMKII as a decoder of Ca2+ oscillations is misleading and suggest experimental tests with rescaled Ca4-CaM concentrations.
- De Koninck P, Schulman H: Sensitivity of CaM kinase II to the frequency of Ca2+ oscillations. Science. 1998, 279 (5348): 227-230. 10.1126/science.279.5348.227.View ArticlePubMedGoogle Scholar
- Dupont G, Houart G, De Koninck P: Sensitivity of CaM kinase II to the frequency of Ca2+ oscillations: a simple model. Cell Calcium. 2003, 34 (6): 485-497. 10.1016/S0143-4160(03)00152-0.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.