A Simulation Study of Calcium Dynamics Features Caused by Exchange between the Cytosol and Organellar Stores of Neurons |
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Authors: | T S Novorodovskaya |
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Institution: | (1) Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark;(2) Institute for Systems Analysis and Informatics, ‘A. Ruberti’ National Research Council, Rome, Italy;(3) Department of Biostatistics, Novo Nordisk A/S, Novo Alle 9F2.23, 2880 Bagsvaerd, Denmark |
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Abstract: | The objects of the study were single-compartment mathematical models corresponding to a fragment of the dendrite of a cerebellar
Purkinje neuron. The fragments contained the mitochondria (model 1) or a cistern of the endoplasmic reticulum, ER (model 2),
functioning as calcium stores. With simulating single excitatory synaptic actions, we examined the dependence of the dynamics
of intracellular Ca2+ levels on the maximum rate of Ca2+ exchange between the cytosol and these stores, as well as on the intensity of the diffusion flow into adjacent organelle-free
regions. The plasma membrane of the compartment had ion channels (including those of the synaptic current) and the calcium
pump characteristic of the mentioned neurons. The model equations took into account Ca2+ exchange between the cytosol, extracellular environment, and organellar stores, as well as the diffusion process. In model
1, the mitochondria exchanged Ca2+ with the cytosol through the uniporter and sodium-calcium exchanger; mitochondrial processes, such as the tricarboxylic acid
cycle and aerobic cellular respiration, were also included. In model 2, the ER membrane had the calcium pump, leak channels,
and channels of calcium-induced and inositol-3-phosphate-dependent Ca2+ release. The stores (mitochondria or ER) occupied 36% of the total volume of the compartment. An increase in the maximum
rate of calcium exchange with the stores led to a proportional decrease in the peak Ca2+ concentrations in the cytosol (Ca2+]i), more pronounced in the case of the ER; the Ca2+ concentration in both types of stores increased significantly. Due to the higher storage rate, the ER was able to absorb
several times greater amounts of Ca2+ than the mitochondria did. With smaller diffusion flux (e.g., similarly to the case of diffusion from a larger-sized head
into the neck of the dendritic spine), the intensity of cytosolic transients increased at fixed kinetics of flux exchange
with the stores. Therefore, the organellar stores can significantly modulate not only the intensity but also the time course
of changes in the intracellular Ca2+ levels. |
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