Kavain, the Major Constituent of the Anxiolytic Kava Extract, Potentiates GABAA Receptors: Functional Characteristics and Molecular Mechanism
Fig 4
Flumazenil-insensitive kavain potentiation has less-than-additive effect on diazepam action.
Top, Representative traces demonstrating responses to control (10 μM GABA); control and 1 μM diazepam; control, 1 μM diazepam and 10 μM flumazenil; control and 10 μM flumazenil; control and 300 μM kavain; control, 300 μM kavain and 10 μM flumazenil; and control, 300 μM kavain and 1 μM diazepam. Bottom, The modulatory effect of diazepam, flumazenil and kavain at α1β2γ2L GABAARs (n = 5). Kavain potentiation was unchanged in the presence of flumazenil (G + K vs. G + K + F; p > 0.05; paired t test). The combination of kavain and diazepam (G + K + D) resulted in greater potentiation than diazepam (G + D; p < 0.001; paired t test) and kavain (G + K; p < 0.0001; paired t test) alone, but the effect was less than the expected additive modulatory effect (dotted line). Data are normalised to the current responses elicited by 10 μM GABA, and are presented as mean ± SEM.