A simplified model of CaMKII activation in the cytosol of dendritic spines
This work presents a simplified model of Ca++/calmodulin-activated kinase II (CaMKII) activation in a single, "well-mixed" volume. The model integrates the N-methyl-D-aspartate receptor (NMDAR) current model developed by Shouval et al. [Shouval et al., 2002], the calmodulin and calbindin models developed by Faas et al. [Faas et al., 2011], and the infinite-subunit holoenzyme approximation (ISHA) developed by Michalski and Loew [Michalski and Loew, 2012]. Models for voltage-sensitive calcium channel (VSCC) currents and the modulation thereof in the presence of added ethylene glycol bis(beta-aminoethyl ether)-N, N, N', N'-tetraacetic acid (EGTA) are developed based on experimental data. Once calibrated against control data in experiments, the model can generally account for CaMKII activation time course in the cytosol of dendritic spines, during both synaptic input via glutamate uncaging and depolarization, with and without added EGTA or 1,2-bis(o-aminophenoxy)ethane-N, N, N', N'-tetraacetic acid (BAPTA). Rationale behind the model, its limitations and inaccuracies, and possible improvements are also discussed.
Giordano, Purdue University.
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