Agonist Fluctuation Maintained Calcium Signaling in a Mesoscopic System

Agonist Fluctuation Maintained Calcium Signaling in a Mesoscopic System

Lin Ji (Capital Normal University, China) and Haiyan Wang (Capital Normal University, China)
DOI: 10.4018/978-1-60960-064-8.ch011
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Signals in transduction cascades are widely exposed to stochastic influences. In this work, we investigate the effects of agonist release noises on calcium signaling. Besides the usually considered “amplitude noise”, the case of “frequency noise” is also discussed. Simulation results show that the transduction cascades may amplify these noises when its intensity is bigger than certain critical value. The amplified noise show constructive effect to maintain the calcium signaling in critical signal-free cases. Moreover, the signal is more sensitive to the “frequency noise” than to the “amplitude noise”. This suggests frequency fluctuations in signaling cascades may have greater influence than the amplitude ones, which is an important finding for signal transduction in complex pathways. Since biological systems are inherently stochastic, this work demonstrates how the calcium system takes advantage of the environmental fluctuations to maintain signaling, and therefore provide effective, sensitive signal communication.
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Agonist influences the Ca2+ signaling through many pathways such as Ca2+-phosphatidylinositol (PI) pathway, NMDA receptor mediated synapses, derndritic calcium action potentials, and Ca2+ liberated by Ca2+ phenomena linked or not to the role of ryanodine receptors of the intracellular endoplasmic reticulum. Here, we employ the receptor-controlled model for intracellular Ca2+ signaling in hepatocytes proposed by Cuthbertson et al. (1991). In this model, the calcium signal (oscillation) is triggered by the binding of agonists (hormone or neurotransmitter) to their receptors, which is the basic signaling mechanism for most of the calcium signaling systems. The influence of agonist is expressed by its concentration. The system dynamics can be described by the following equations:


For simplicity, it is assumed that [DAG] and [IP3] increase with the same rate, i.e., [DAG] = [IP3]. [Gα-GDP] and [PLC] are determined by the relations: , in which G0 and P0 are the total concentration of G-proteins and PLC, respectively. Parameter kg is proportional to the agonist concentration. ld and lc are “leak” terms of the signaling dynamics, which keeps the cell at its basal level of [DAG] and [Ca2+]i, respectively, in the absence of external stimuli. kp, hp and kd are supposed to take the form: where kn = kp,hp,or kd. Detailed information about the model can be found in Ref (Cuthbertson et al., 1991).

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