G-PROTEIN ACTIVATION KINETICS AND SPILLOVER OF GAMMA-AMINOBUTYRIC-ACID MAY ACCOUNT FOR DIFFERENCES BETWEEN INHIBITORY RESPONSES IN THE HIPPOCAMPUS AND THALAMUS

We have developed a model of gamma-aminobutyric acid (GABA)ergic synaptic transmission mediated by GABA(A) and GABA(B) receptors, including cooperativity in the guanine nucleotide binding protein (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 spillover resulted in 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, prolonged activation of the receptors was due to high-frequency release conditions, This model provides insights into the function of GABA(B) receptors in normal and epileptic discharges.