Neuronal calcium wave propagation varies with changes in endoplasmic reticulum parameters: a computer model.
Neural Comput
; 27(4): 898-924, 2015 Apr.
Article
en En
| MEDLINE
| ID: mdl-25734493
ABSTRACT
Calcium (Ca²âº) waves provide a complement to neuronal electrical signaling, forming a key part of a neuron's second messenger system. We developed a reaction-diffusion model of an apical dendrite with diffusible inositol triphosphate (IP3), diffusible Ca²âº, IP3 receptors (IP3Rs), endoplasmic reticulum (ER) Ca²âº leak, and ER pump (SERCA) on ER. Ca²âº is released from ER stores via IP3Rs upon binding of IP3 and Ca²âº. This results in Ca²âº-induced-Ca²âº-release (CICR) and increases Ca²âº spread. At least two modes of Ca²âº wave spread have been suggested a continuous mode based on presumed relative homogeneity of ER within the cell and a pseudo-saltatory model where Ca²âº regeneration occurs at discrete points with diffusion between them. We compared the effects of three patterns of hypothesized IP3R distribution (1) continuous homogeneous ER, (2) hotspots with increased IP3R density (IP3R hotspots), and (3) areas of increased ER density (ER stacks). All three modes produced Ca²âº waves with velocities similar to those measured in vitro (approximately 50-90 µm /sec). Continuous ER showed high sensitivity to IP3R density increases, with time to onset reduced and speed increased. Increases in SERCA density resulted in opposite effects. The measures were sensitive to changes in density and spacing of IP3R hotspots and stacks. Increasing the apparent diffusion coefficient of Ca²âº substantially increased wave speed. An extended electrochemical model, including voltage-gated calcium channels and AMPA synapses, demonstrated that membrane priming via AMPA stimulation enhances subsequent Ca²âº wave amplitude and duration. Our modeling suggests that pharmacological targeting of IP3Rs and SERCA could allow modulation of Ca²âº wave propagation in diseases where Ca²âº dysregulation has been implicated.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Simulación por Computador
/
Señalización del Calcio
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Retículo Endoplásmico
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Modelos Neurológicos
/
Neuronas
Límite:
Animals
Idioma:
En
Revista:
Neural Comput
Asunto de la revista:
INFORMATICA MEDICA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos