" ... In this work, we have combined stochastic computational modeling and a systematic pharmacological study of different signaling pathways to investigate their impact during short-term adaptation (STA). ... These results suggest that G-coupled receptors (GPCRs) cycling is involved with the occurrence of STA. To gain insights on the dynamical aspects of this process, we developed a stochastic computational model. The model consists of the olfactory transduction currents mediated by the cyclic nucleotide gated (CNG) channels and calcium ion (Ca2+)-activated chloride (CAC) channels, and the dynamics of their respective ligands, cAMP and Ca2+, and it simulates the EOG (electroolfactogram) results obtained under different experimental conditions through changes in the amplitude and duration of cAMP and Ca2+ response, two second messengers implicated with STA occurrence. The model reproduced the experimental data for each pharmacological treatment and provided a mechanistic explanation for the action of GPCR cycling in the levels of second messengers modulating the levels of STA. All together, these experimental and theoretical results indicate the existence of a mechanism of regulation of STA by signaling pathways that control GPCR cycling and tune the levels of second messengers in OSNs, and not only by CNG channel desensitization as previously thought. "
Model Type: Channel/Receptor; Molecular Network
Cell Type(s): Olfactory receptor GLU cell
Model Concept(s): Ion Channel Kinetics; Detailed Neuronal Models; Signaling pathways; Calcium dynamics; Olfaction
Simulation Environment: COPASI
Implementer(s): Simoes-de-Souza, Fabio [fabio.souza at ufabc.edu.br]
References:
Antunes G, Sebastião AM, Simoes de Souza FM. (2014). Mechanisms of regulation of olfactory transduction and adaptation in the olfactory cilium. PloS one. 9 [PubMed]