G-Protein Activation Kinetics And Spill-Over Of Gaba May Account For Differences Between Inhibitory
We have developed a model of GABAergic synaptic transmission mediated by GABA A and GABA B receptors, including cooperativity in the G-protein cascade mediating the activation of K + channels by GABA B receptors. If the binding of several G-proteins is needed to activate the K + channels, then only a prolonged activation of GABA B receptors evoked detectable currents. This could occur if strong stimuli evoked release in adjacent terminals, and the spill-over resulted in the prolonged activation of the receptors, leading to inhibitory responses similar to those observed in hippocampal slices. The same model also reproduced thalamic GABA B responses to high-frequency bursts of stimuli. In this case, the prolonged activation of the receptors was due to high-frequency release conditions. This model provides new insights into the function of GABA B receptors in normal and epileptic discharges.