Neuronal dendrite calcium wave model (Neymotin et al, 2015)

"... We developed a reaction-diffusion model of an apical dendrite with diffusible inositol triphosphate (IP3 ), diffusible Ca2+, IP3 receptors (IP3 Rs), endoplasmic reticulum (ER) Ca2+ leak, and ER pump (SERCA) on ER. ... At least two modes of Ca2+ wave spread have been suggested: a continuous mode based on presumed relative homogeneity of ER within the cell; and a pseudo-saltatory model where Ca2+ regeneration occurs at discrete points with diffusion between them. We compared the effects of three patterns of hypothesized IP3 R distribution: 1. continuous homogeneous ER, 2. hotspots with increased IP3R density (IP3 R hotspots), 3. areas of increased ER density (ER stacks). All three modes produced Ca2+ waves with velocities similar to those measured in vitro (~50 - 90µm /sec). ... The measures were sensitive to changes in density and spacing of IP3 R hotspots and stacks. ... An extended electrochemical model, including voltage gated calcium channels and AMPA synapses, demonstrated that membrane priming via AMPA stimulation enhances subsequent Ca2+ wave amplitude and duration. Our modeling suggests that pharmacological targeting of IP3 Rs and SERCA could allow modulation of Ca2+ wave propagation in diseases where Ca2+ dysregulation has been implicated. "

Model Type: Dendrite

Cell Type(s): Hippocampus CA1 pyramidal GLU cell; Hippocampus CA3 pyramidal GLU cell; Neocortex L5/6 pyramidal GLU cell; Neocortex L2/3 pyramidal GLU cell

Currents: I T low threshold; I A; I K; I K,Ca; I CAN; I Sodium; I Calcium; I_SERCA; I_KD; Ca pump

Receptors: AMPA

Transmitters: Glutamate

Model Concept(s): Calcium waves; Reaction-diffusion

Simulation Environment: NEURON

Implementer(s): Neymotin, Sam [Samuel.Neymotin at]; McDougal, Robert [robert.mcdougal at]; Sherif, Mohamed [ at]


Neymotin SA et al. (2015). Neuronal calcium wave propagation varies with changes in endoplasmic reticulum parameters: a computer model. Neural computation. 27 [PubMed]

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