Kinetic Models of Modulatory Effects of GABAergic Transmission: Computational Studies
Barkume, Shanna G.
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This research used a computational approach to study a chemical kinetic scheme for the GABAAreceptor in the presence and absence of the pharmacological modulator propofol (2,6-diisopropylphenol), which is a general intravenous anesthetic.The goal of study was to investigate the properties of synaptic transmission in the presence of propofol via a detailed kinetic model. For the research, the NEURON SIMULATION PACKAGE (www.neuron.yale.edu) was employed to model the transformations of kinetic states via a system of ordinary differential equations. It was demonstrated that for continuous GABA release into the synapse propofol shifts the dose-response curve to the left when compared to a control, and increases the steady-state conductance of the cell, indicating that propofol prolongs inhibitory post-synaptic currents. The periodic perturbation of the system was also studied for varying frequencies of GABA release. It was shown that for periodic GABA release of frequencies between 10-50 Hz, propofol decreases the number of GABAa receptors in the open, conducting state. The suppression of the low end of gamma band oscillations (approximately 40 Hz) by propofol could be linked to its actions as a general anesthetic.