"... 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 nki.rfmh.org]; McDougal, Robert [robert.mcdougal at yale.edu]; Sherif, Mohamed [mohamed.sherif.md at gmail.com]
References:
Neymotin SA et al. (2015). Neuronal calcium wave propagation varies with changes in endoplasmic reticulum parameters: a computer model. Neural computation. 27 [PubMed]