title: A novel explanation for observed CaMKII dynamics in dendritic spines with added EGTA or BAPTA.
abstract: We present a simplified reaction network in a single well-mixed volume that captures the general features of CaMKII dynamics observed during both synaptic input and spine depolarization. Our model can also account for the greater-than-control CaMKII activation observed with added EGTA during depolarization. Calcium input currents are modeled after experimental observations, and existing models of calmodulin and CaMKII autophosphorylation are used. After calibration against CaMKII activation data in the absence of chelators, CaMKII activation dynamics due to synaptic input via n-methyl-d-aspartate receptors are qualitatively accounted for in the presence of the chelators EGTA and BAPTA without additional adjustments to the model. To account for CaMKII activation dynamics during spine depolarization with added EGTA or BAPTA, the model invokes the modulation of CaV2.3 (R-type) voltage-dependent calcium channel (VDCC) currents observed in the presence of EGTA or BAPTA. To our knowledge, this is a novel explanation for the increased CaMKII activation seen in dendritic spines with added EGTA, and suggests that differential modulation of VDCCs by EGTA and BAPTA offers an alternative or complementary explanation for other experimental results in which addition of EGTA or BAPTA produces different effects. Our results also show that a simplified reaction network in a single, well-mixed compartment is sufficient to account for the general features of observed CaMKII dynamics.
authors.affiliation: Department of Physics, Purdue University, West Lafayette, Indiana. Electronic address: matmat@purdue.edu.
authors.forename: Matt
authors.initials: M
authors.lastname: Matolcsi
authors.affiliation: Department of Physics, Auburn University, Auburn, Alabama.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Giordano
mesh_terms: D000818:Animals; D020908:Calcium Channels, R-Type / Q000737:chemistry / Q000378:metabolism; D065096:Calcium Chelating Agents / Q000737:chemistry / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000737:chemistry / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D008954:Models, Biological
chemical_list: D020908:Calcium Channels, R-Type; D065096:Calcium Chelating Agents; D004533:Egtazic Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid