Figure 4.

Use-dependent and use-independent inhibition of NMDA receptor channels by steroids. The Figure shows examples of records obtained from HEK293 cells transfected with NR1 and NR2B subunits. (A) On the left, response to co-application of 300 µmol·L⁻¹ PA-6 and 1 mmol·L⁻¹ glutamate (Glu) made after the onset of the response to the agonist was inhibited by 97% and recovered from the inhibition on a slow timescale. In the middle, the onset of the response to application of 1 mmol·L⁻¹ glutamate made immediately after pre-application of 300 µmol·L⁻¹ PA-6 for 10 s was rapid, similar to the control glutamate response. (B) On the left, response to co-application of 30 µmol·L⁻¹ PA-27 and 1 mmol·L⁻¹ glutamate (Glu) made after the onset of the response to the agonist was inhibited by 98% and recovered from the inhibition on a slow timescale. In the middle, the onset of the response to application of 1 mmol·L⁻¹ glutamate made immediately after pre-application of 30 µmol·L⁻¹ PA-27 for 10 s was slow, similar to the recovery after PA-27 and glutamate co-application. (C) On the left, response to co-application of 200 µmol·L⁻¹ PA-22 and 1 mmol·L⁻¹ glutamate (Glu) made after the onset of the response to the agonist was inhibited by 95% and recovered from the inhibition on a slow timescale. In the middle, the onset of the response to application of 1 mmol·L⁻¹ glutamate made immediately after pre-application of 200 µmol·L⁻¹ PA-22 for 10 s was complex characterized by biphasic response – the first being fast and the second slow. (A-C) On the right, recovery from inhibition induced by steroid and glutamate co-application (in red) and steroid pre-application (in black) are displayed overlaid to show the difference in the rate of recovery. Note that the recovery from inhibition was similar for all three steroids; in the case of co-application, there were differences in the recovery after the steroid application.