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Modeling the Effect of Cooperativity on Ligand-Driven Fluctuations of Metabotropic Glutamate Receptors
Liu, Jeffrey Y
Liu, Jeffrey Y
Abstract
The metabotropic glutamate receptors (mGluRs) are a family of dimeric G-protein coupled receptors (GPCR) that play a significant role in the modulation of synaptic transmission and excitability in neuronal cells [10]. Upon formation of mGluR dimers, protomer binding sites interact cooperatively with ligands, leading to receptor activation [5,9,10]. The dimer typically activates with full receptor occupancy, so the noise output of the system is assumed to scale in proportion to the number of activated dimers [2]. While the characterization of noise is well appreciated, the connection between cooperativity and noise has received less attention [1,2]. We examine the effects of cooperativity on concentration fluctuations of active mGluR in synaptic complexes. The fluctuating dynamics are well-approximated by the solution to the chemical langevin equation; we derive chemical langevin equations for the fluctuating dynamics of glutamate binding to mGluRs, and use the associated stochastic system to determine the magnitude of fluctuations for different parameter values (e.g. dissociation constants and concentration). Cooperative binding increases sensitivity of the system to small changes in concentration of glutamate and can decrease active mGluR fluctuations. This raises the question of whether or not cooperativity effects on concentration fluctuations are important for modulating synaptic activity.
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2015-05-01
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Interdisciplinary Studies