Modeling the activity of the dopamine signaling pathway by combination of analog electrical circuit and mathematical approaches

Abstract

This paper demonstrates the application of the system biology principles on the example of the dopamine signaling pathway in neurons. Presented model is based on two approachescytomorphic electronic circuits and mathematical modeling. Transcription and phosphorylation of DARPP-32 was modeled by analog circuit, based on well-known approaches presented in [1]. It was shown that application of circuit helps to receive signal oscillations that close to described ones in real biological systems. This combination on the one hand gives possibility to simplify calculations, on another to show this signaling pathway dynamics. The expected effect of changes in the functioning of calcium channels is considered, and the mathematical model of the interaction of system components is proposed. The average frequency of calcium current oscillations due to the presence of dopamine was 30 Hz in presented model, that is consistent with the literature, where the frequency of such oscillations is up to several tens of Hz. All presented results shows good correlation with known data, which already published today.

Computational investigation of the dynamic control of cAMP signaling by PDE4 isoform types

“…Various mechanistic computational models have been developed previously to understand cAMP signaling pathway dynamics. These models have investigated, among others, the diffusion and stochastic effects on the information flow through PKA signaling (30), the dynamics of calcium-induced cAMP signaling (31)(32)(33)(34), the influence of receptor protein kinase and G-protein-coupled receptor crosstalk (35), and the localization of cAMP signaling in subcellular domains (36)(37)(38)(39). Despite their important role in inactivating cAMP, cAMP-degrading PDE enzymes and their isoforms, which respond differently to feedback mechanisms, are not always included in the computational modeling efforts.…”