Agonist Dissociation from Diliganded-open AChRs
Construct . | β2ACh . | α2ACh . | τb (observed) . | τb (calculated) . |
|---|---|---|---|---|
| s−1 | s−1 | ms | ms | |
| Wild-type | 50,000 | 2,000 | 0.99 | 1.05 |
| δS12′G | 60,700 | 1,807 | 1.67 | 1.30 |
| δS12′C | 108,950 | 346 | 6.42 | 9.85 |
| δS12′T | 129,770 | 351 | 6.87 | 11.03 |
| δS12′V | 149,030 | 125 | 12.62 | 34.37 |
| δS12′N | 192,410 | 102 | 13.77 | 51.52 |
| δL9′T | 50,000 | 84 | 8.00 | 25.07 |
| αD97N | 134,000 | 2,379 | 1.79 | 1.67 |
| αD97C | 265,500 | 2,172 | 2.12 | 3.16 |
| αD97M | 417,500 | 2,255 | 2.13 | 4.54 |
| αD97Y | 698,000 | 1,992 | 3.01 | 8.25 |
| δL9′T-αD97C | 265,500 | 87 | 12.31 | 79.43 |
| δL9′T-αD97E | 1,226,000 | 82 | 9.38 | 341.53 |
| δL9′T-αD97Q | 3,000,000 | 81 | 11.97 | 835.17 |
| δL9′T-αD97A | 6,895,000 | 69 | 17.59 | 2,230.96 |
Construct . | β2ACh . | α2ACh . | τb (observed) . | τb (calculated) . |
|---|---|---|---|---|
| s−1 | s−1 | ms | ms | |
| Wild-type | 50,000 | 2,000 | 0.99 | 1.05 |
| δS12′G | 60,700 | 1,807 | 1.67 | 1.30 |
| δS12′C | 108,950 | 346 | 6.42 | 9.85 |
| δS12′T | 129,770 | 351 | 6.87 | 11.03 |
| δS12′V | 149,030 | 125 | 12.62 | 34.37 |
| δS12′N | 192,410 | 102 | 13.77 | 51.52 |
| δL9′T | 50,000 | 84 | 8.00 | 25.07 |
| αD97N | 134,000 | 2,379 | 1.79 | 1.67 |
| αD97C | 265,500 | 2,172 | 2.12 | 3.16 |
| αD97M | 417,500 | 2,255 | 2.13 | 4.54 |
| αD97Y | 698,000 | 1,992 | 3.01 | 8.25 |
| δL9′T-αD97C | 265,500 | 87 | 12.31 | 79.43 |
| δL9′T-αD97E | 1,226,000 | 82 | 9.38 | 341.53 |
| δL9′T-αD97Q | 3,000,000 | 81 | 11.97 | 835.17 |
| δL9′T-αD97A | 6,895,000 | 69 | 17.59 | 2,230.96 |
The channel-opening (β2) and -closing (α2) rate constants with ACh as the agonist were calculated from the corresponding measured values for choline (Table II) assuming Φ = 1 for the transmitter binding sites. The wild-type AChR β2 and α2 values are from Salamone et al. (1999). τb (observed) is the burst duration measured at 1 μM ACh. τb (calculated) was generated using Eq. 4, the β2 and α2 values in the table, and k−2 = 45,216 s−1 (see Fig. 5 and materials and methods).