Kinetics of inhibition of hNaV1.7 by nTp1a, sTp1a-NH2, sTp1a-OH, and rGly-Tp1a
Tp1a was applied at 0.2, 2, and 20 nM (nTp1a and sTp1a-NH2) or 1.5, 15, and 150 nM (sTp1a-OH and rGly-Tp1a), then sodium currents were measured. The kinetics of inhibition and recovery of inhibition were determined from the I/Imax as a function of time from traces shown in Fig. 8, fitted to a single exponential fit. Values are from at least three independent experiments (mean ± S.D.).
| Concentration | Kon | Koff | Kd |
|---|---|---|---|
| nM-1s−1 | s−1 | nM | |
| nTp1a | |||
| 0.2 nM | 4.1 ± 1.3 × 10−5 | 0 | 0 |
| 2.0 nM | 5.1 ± 2.2 × 10−6 | 0 | 0 |
| 20 nM | 3.4 ± 1.7 × 10−4 | 0 | 0 |
| sTp1a-NH2 | |||
| 0.2 nM | 2.4 ± 0.5 × 10−5 | 0 | 0 |
| 2.0 nM | 2.7 ± 1.2 × 10−6 | 0 | 0 |
| 20 nM | 3.6 ± 0.6 × 10−4 | 0 | 0 |
| sTp1a-OH | |||
| 1.5 nM | 2.0 ± 0.2 × 10−4 | ND | 1.5 ± 0.1 |
| 15 nM | 1.9 ± 0.4 × 10−5 | ND | 16.2 ± 0.3 |
| 150 nM | 4.4 ± 1.7 × 10−5 | 3.1 ± 0.2 × 10−4 | 7.1 ± 0.5 |
| rGly-Tp1a | |||
| 1.5 nM | 2.3 ± 1.3 × 10−4 | ND | 1.5 ± 0.2 |
| 15 nM | 2.3 ± 0.5 × 10−5 | ND | 15.13 ± 0.03 |
| 150 nM | 2.2 ± 0.3 × 10−5 | 3.5 ± 0.5 × 10−4 | 15.84 ± 0.05 |
ND, not determined.