Figure 7.

Responses of concatemeric receptors to the positive modulator neurosteroid 3α5αP. (A) Responses to 0.3 µM GABA alone (black, smallest trace) and increasing concentrations of 3α5αP, represented by increasingly lighter shades of grey. (B) Sample responses of an oocyte expressing α1 +β2 +γ2L to 2 µM GABA and increasing 3α5αP concentrations. (C) 3α5αP concentration-response relationship for eight oocytes expressing concatemeric α4/δ-containing receptors and four oocytes expressing α1 +β2 +γ2L receptors. Solid lines represent fits to the Hill equation. Parameters for the fits are given in the Results. (D) Representative responses to low steroid concentration, showing that both synaptic-like and extrasynaptic-like receptors respond detectably. (E) Representative responses to saturating GABA concentration (30 µM for left traces and 100 µM for right traces) in the absence and presence of 1 µM 3α5αP. Weak GABA efficacy was correlated with stronger potentiation at a high GABA concentration. (F) Responses to the higher efficacy agonist THIP are potentiated to the same maximum level as responses to saturating GABA. Oocytes expressing concatemeric receptors were challenged with 30 µM GABA, 30 µM GABA plus 1 µM 3α5αP, 1 mM THIP and 1 mM THIP plus 1 µM 3α5αP. All responses are normalized to the response to GABA alone in the same oocyte.