Computational Model of the Insect Pheromone Transduction Cascade

Abstract

A biophysical model of receptor potential generation in the male moth olfactory receptor neuron is presented. It takes into account all pre-effector processes—the translocation of pheromone molecules from air to sensillum lymph, their deactivation and interaction with the receptors, and the G-protein and effector enzyme activation—and focuses on the main post-effector processes. These processes involve the production and degradation of second messengers (IP3 and DAG), the opening and closing of a series of ionic channels (IP3-gated Ca2+ channel, DAG-gated cationic channel, Ca2+-gated Cl− channel, and Ca2+- and voltage-gated K+ channel), and Ca2+ extrusion mechanisms. The whole network is regulated by modulators (protein kinase C and Ca2+-calmodulin) that exert feedback inhibition on the effector and channels. The evolution in time of these linked chemical species and currents and the resulting membrane potentials in response to single pulse stimulation of various intensities were simulated. The unknown parameter values were fitted by comparison to the amplitude and temporal characteristics (rising and falling times) of the experimentally measured receptor potential at various pheromone doses. The model obtained captures the main features of the dose–response curves: the wide dynamic range of six decades with the same amplitudes as the experimental data, the short rising time, and the long falling time. It also reproduces the second messenger kinetics. It suggests that the two main types of depolarizing ionic channels play different roles at low and high pheromone concentrations; the DAG-gated cationic channel plays the major role for depolarization at low concentrations, and the Ca2+-gated Cl− channel plays the major role for depolarization at middle and high concentrations. Several testable predictions are proposed, and future developments are discussed.

Calcium Activates a Chloride Conductance Likely Involved in Olfactory Receptor Neuron Repolarization in the MothSpodoptera littoralis

“…The latter observation is in good agreement with the involvement of a Cl Ϫ current during ORN responses and supports the hypothesis of a Cl Ϫ entry within the ORN dendrite, leading to ORN repolarization. However the present evidence is not fully unequivocal [see discussion in the study by Gu et al (2009)]. Previous Cl Ϫ measurements were described as rough estimates of relative concentrations of Cl Ϫ , so only new measurements of intracellular and extracellular Cl Ϫ concentrations can provide definitive evidence on the role of I Cl,Ca in moth pheromone transduction.…”

“…The Ca 2ϩ rise opens Cl Ϫ channels (Kleene, 2002), resulting in an excitatory Cl Ϫ current (Kurahashi and Yau, 1993;Lowe and Gold, 1993;Zhainazarov and Ache, 1995) that can be the major component of the receptor current (Reisert et al, 2003;Boccaccio and Menini, 2007). The similarities in transduction between vertebrate and insect ORNs led us develop a model of insect transduction in which the Cl Ϫ current is also depolarizing (Gu et al, 2009). However, an outward Cl Ϫ flux has not been demonstrated in insect ORNs [assumption C in the study by Gu et al (2009)].…”

“…The similarities in transduction between vertebrate and insect ORNs led us develop a model of insect transduction in which the Cl Ϫ current is also depolarizing (Gu et al, 2009). However, an outward Cl Ϫ flux has not been demonstrated in insect ORNs [assumption C in the study by Gu et al (2009)]. …”

Recent Advances in Olfactory Receptor (OR) Biosensors and Cell Signaling Cascade Amplification Systems

“…The intracellular signal transduction depends on different series of cascade reactions. (86,87) The amount of GPCR expressed on single cells is very low, and the interaction generated from the binding of receptors and ligands is very weak, but the weak binding signal can be captured eventually by the electrodes because the binding of receptors and ligands activates the amplification process of the intracellular G protein, causing a series of changes in electrochemical signals. This realized the identification and detection of gas molecules and also confirmed that the G protein signal amplification system could be used to sense the signals transmitted by the GPCRs of other species.…”

Reconstruction, Identification and Implementation Methods for Spiking Neural Circuits

“…Sensory processing systems have been identified using detailed biophysical models (Gu et al, 2009, Song et al, 2009 as well as phenomenological models (Friederich et al, 2009a, Geffen et al, 2009, Kim et al, 2011, Pillow and Simoncelli, 2006, Slee et al, 2005.…”