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- W2027509953 abstract "Experiments by Lee et al. (Lee et al., 2009) provide compelling evidence of spatially inhomogeneous reactant distributions in dendritic spines. We have built a reaction-diffusion model of a dendritic spine using the calmodulin activation kinetics developed by Faas et al. (Faas et al., 2011). Upon calcium influx from voltage-sensitive calcium channels, we find spatial inhomogeneities lasting 2 ms in the distribution of calmodulin with N-lobe-bound calcium, but no significant inhomogeneities in the distributions of calmodulin with C-lobe-bound calcium or calbindin. In the presence of 5 mM EGTA, the spatial inhomogeneity in the concentration of calmodulin with N-lobe-bound calcium persists for 1 ms, eventually becoming restricted to the outer 200 nm of the spine at 20 mM EGTA. Calmodulin with C-lobe-bound calcium continues to penetrate to the interior, but at a lower concentration and with an inhomogeneous distribution. In the presence of 5 mM and 20 mM BAPTA, concentrations of both species drop sharply and they are not able to diffuse to the interior of the spine. We believe that these spatial inhomogeneities (arising during calcium influx) can assist in explaining the results presented by Lee et al. Furthermore, our work forms a basis for a spatially-resolved reaction-diffusion model of dendritic spines that includes the reactions underlying the activation, phosphorylation and dephosphorylation of CaMKII, as well as long-term potentiation, and long-term depression.1. S-J. R. Lee et al., Activation of CaMKII in single dendritic spines during long-term potentiation. NATURE, 458(7236):299-U58, MAR 19 2009.2. G. C. Faas., Calmodulin as a direct detector of Ca2+ signals. NATURE Neuroscience, 14(3):301-304, MAR 2011." @default.
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- W2027509953 date "2013-01-01" @default.
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- W2027509953 title "Spatiotemporal Dynamics of Calmodulin in Dendritic Spines during Calcium Influx" @default.
- W2027509953 doi "https://doi.org/10.1016/j.bpj.2012.11.921" @default.
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