TABLE 3.
EC50 and Hill coefficient values (mean ± S.E.) for mutations in the muscle-type receptor
Mutations identified as Leu and Val represent recovery of the wild-type receptor by nonsense suppression. Mutations denoted with an asterisk have the βL9′S mutation. Lah, α-hydroxyleucine; Vah, α-hydroxyvaline.
| Mutation | Drug | EC50 | Hill |
|---|---|---|---|
| μm | |||
| Wild type | ACh | 16.0 ± 0.3 | 1.3 ± 0.1 |
| γL119Leu/δL121Leu | ACh | 16.0 ± 0.5 | 1.5 ± 0.1 |
| γL119Lah/δL121Lah | ACh | 230 ± 6 | 1.5 ± 0.1 |
| Wild type* | ACh | 0.61 ± 0.04 | 1.4 ± 0.1 |
| γL119Leu/δL121Leu* | ACh | 0.31 ± 0.02 | 1.5 ± 0.1 |
| γL119Lah/δL121Lah* | ACh | 9.1 ± 0.7 | 1.6 ± 0.2 |
| Wild type* | Choline | 840 ± 20 | 1.6 ± 0.1 |
| γL119Leu/δL121Leu* | Choline | 780 ± 30 | 1.7 ± 0.1 |
| γL119Lah/δL121Lah* | Choline | 1000.00 ± 0.05 | 1.8 ± 0.1 |
| Wild type* | (±)-Epibatidine | 0.32 ± 0.02 | 1.5 ± 0.1 |
| γL119Leu/δL121Leu* | (±)-Epibatidine | 0.40 ± 0.02 | 1.5 ± 0.1 |
| γL119Lah/δL121Lah* | (±)-Epibatidine | 0.52 ± 0.03 | 1.6 ± 0.1 |
| Wild type* | S-Nicotine | 22.0 ± 0.8 | 1.6 ± 0.1 |
| γL119Leu/δL121Leu* | S-Nicotine | 23 ± 0.7 | 1.7 ± 0.1 |
| γL119Lah/δL121Lah* | S-Nicotine | 230 ± 30 | 2.2 ± 0.5 |
| γV108Val/δV110Val* | ACh | 0.29 ± 0.01 | 1.3 ± 0.1 |
| γV108Vah/δV110Vah* | ACh | 0.41 ± 0.05 | 1.2 ± 0.2 |
| γV108Val/δV110Val* | Choline | 620 ± 20 | 1.4 ± 0.1 |
| γV108Vah/δV110Vah* | Choline | 790 ± 60 | 1.4 ± 0.1 |
| γV108Val/δV110Val* | (±)-Epibatidine | 0.230 ± 0.006 | 1.4 ± 0.1 |
| γV108Vah/δV110Vah* | (±)-Epibatidine | 0.240 ± 0.006 | 1.5 ± 0.1 |
| γV108Val/δV110Val* | S-Nicotine | 15 ± 1 | 1.2 ± 0.1 |
| γV108Vah/δV110Vah* | S-Nicotine | 33 ± 2 | 1.6 ± 0.1 |
| α1G153K* | ACh | 0.0072 ± 0.0007 | 1.3 ± 0.1 |
| α1G153K/γL119Leu/δL121Leu* | ACh | 0.0076 ± 0.0007 | 1.8 ± 0.3 |
| α1G153K/γL119Lah/δL121Lah* | ACh | 0.18 ± 0.02 | 1.3 ± 0.1 |
| α1G153K* | Choline | 30 ± 2 | 1.0 ± 0.1 |
| α1G153K/γL119Leu/δL121Leu* | Choline | 27 ± 2 | 1.1 ± 0.1 |
| α1G153K/γL119Lah/δL121Lah* | Choline | 68 ± 3 | 1.3 ± 0.1 |
| α1G153K* | (±)-Epibatidine | 0.0043 ± 0.0005 | 0.77 ± 0.5 |
| α1G153K/γL119Leu/δL121Leu* | (±)-Epibatidine | 0.0023 ± 0.0004 | 0.74 ± 0.1 |
| α1G153K/γL119Lah/δL121Lah* | (±)-Epibatidine | 0.0096 ± 0.0004 | 1.1 ± 0.1 |
| α1G153K* | S-Nicotine | 0.32 ± 0.03 | 1.4 ± 0.2 |
| α1G153K/γL119Leu/δL121Leu* | S-Nicotine | 0.36 ± 0.04 | 0.95 ± 0.1 |
| α1G153K/γL119Lah/δL121Lah* | S-Nicotine | 6.5 ± 0.5 | 1.3 ± 0.1 |