The neurotransmitter GABA acts on both ionotropic GABA_A and metabotropic GABA_B receptors. The repetitive GABA application on pyramidal neurons in temporal cortex slices makes evident an activity-dependent decrease of the GABA_A-mediated current amplitudes (I_GABA rundown), significantly higher in mesial temporal lobe epilepsy than in control conditions. Repetitive applications of muscimol, a selective agonist of GABAA receptors, induce a larger rundown than GABA, suggesting that GABA_B activation exerts a modulatory action on I_GABA. Thus, our objective was the description of the role of GABA_B receptors in the GABA_A receptor modulation, in different epileptic or control tissues.

In control rat temporal neurons, the co-application of muscimol and baclofen (selective GABA_B agonist) produced a smaller I_GABA rundown than using only muscimol, while co-application of GABA and CGP55845 (selective GABA_B antagonist) significantly increased GABA_A receptor instability. By contrast, in epileptic tissue this modulation was absent. The activation of GABA_B receptors was also able to modify the miniature inhibitory GABAergic synaptic currents recorded from human and rat neurons, reducing in the epileptic tissue the amount of electrical charge flowing through GABA_A receptors in a single synaptic event. We conclude that the activation of GABA_B receptors affects the GABA_A receptors expressed on the same neuron, and this modulation determines in epileptic tissue a lower level of inhibition.