Proceedings of the National Academy of Sciences of the United States of America 92: 9515-9519, 1995
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.