Fitting of macroscopic GluN1/GluN2B current response with and without ifenprodil
The normalized residual sum of squares (indicated as “residual”) were derived from the macroscopic fitting with the gating rates fixed to those derived from MIL fits (Table 2); the desensitization (d) and agonist binding (b+) and unbinding (b-) rates were set as free parameters. The agonist binding rates are in µM−1s−1 and all other rate constants are s−1. The Kd is in µM and calculated as b-/b+. The desensitization rate was constrained to the following range: d1+ and d1- = 0.1–10, d2+ = 5–250, and d2- = 1–25.
| Rates | Experiment | Scheme 1 Linear | Scheme 3 Cyclic Uncoupled | |||
|---|---|---|---|---|---|---|
| Control | Ifenprodil | Control | Ifenprodil | Control | Ifenprodil | |
| b+ | — | — | 1.5 | 3.1 | 2.1 | 3.5 |
| b- | — | — | 2.5 | 1.2 | 4.4 | 1.6 |
| d1+ | — | — | 0.16 | 0.11 | 0.55 | 0.18 |
| d1- | — | — | 0.45 | 0.37 | 0.93 | 0.31 |
| d2+ | — | — | 6.9 | 6.0 | 88 | 16 |
| d2- | — | — | 21 | 7.7 | 19 | 2.3 |
| Residual | — | — | 2.64 × 10−6 | 3.02 × 10−6 | 2.16 × 10−6 | 1.02 × 10−6 |
| Kd | — | — | 1.7 | 0.38 | 2.1 | 0.45 |
| PO (SS) | 0.045 | 0.019 | 0.047 | 0.018 | 0.047 | 0.017 |
| MOT | 0.92 | 0.98 | 0.82 | 0.85 | 0.92 | 0.76 |
| ISS/Ipeak | 0.75 | 0.62 | 0.86 | 0.82 | 0.73 | 0.57 |
Ipeak, peak current; ISS, steady-state current; MOT, mean open time; Po, open probability.