Table 2.
Effects of M4 C-terminal deletions on nAChR function and expression
| Dose responsea | ||||
|---|---|---|---|---|
| Deletion(s) | EC50 (μM) | pEC50 (M) | Hill slope | n |
| α subunit | ||||
| WT: …LAVFAGRLIELNQQG | 7.61 | 5.12 ± 0.07 | 1.70 ± 0.47 | 50 |
| Δ1: …LAVFAGRLIELNQQ | 6.86 | 5.17 ± 0.06 | 2.66 ± 0.67 | 9 |
| Δ2: …LAVFAGRLIELNQ | 6.37 | 5.20 ± 0.07 | 2.62 ± 0.54 | 9 |
| Δ3: …LAVFAGRLIELN | 7.14 | 5.15 ± 0.07 | 2.36 ± 0.38 | 8 |
| Δ4: …LAVFAGRLIEL | 8.49 | 5.08 ± 0.07 | 2.13 ± 0.44 | 8 |
| Δ5: …LAVFAGRLIE | 11.8 | 4.93 ± 0.04b | 1.65 ± 0.33 | 10 |
| Δ6: …LAVFAGRLI | 12.3 | 4.91 ± 0.04b | 1.59 ± 0.25 | 10 |
| Δ7: …LAVFAGRL | 12.7 | 4.90 ± 0.06b | 1.54 ± 0.15 | 10 |
| Δ8: …LAVFAGR | 14.7 | 4.84 ± 0.07b | 1.46 ± 0.29 | 10 |
| Δ9: …LAVFAG | 14.9 | 4.83 ± 0.08b | 1.77 ± 0.35 | 10 |
| Δ10: …LAVFA | 21.4 | 4.68 ± 0.08b | 1.35 ± 0.12 | 10 |
| Δ11: …LAVF | 23.0 | 4.65 ± 0.09b | 1.69 ± 0.36 | 10 |
| Δ12: …LAV | No currentc | - | - | 8 |
| β subunit | ||||
| WT: …LVIFLDATYHLPPPDPFP | 7.61 | 5.12 ± 0.07 | 1.70 ± 0.47 | 50 |
| Δ1: …LVIFLDATYHLPPPDPF | 9.77 | 5.02 ± 0.09 | 1.59 ± 0.08 | 13 |
| Δ2: …LVIFLDATYHLPPPDP | 9.65 | 5.02 ± 0.05 | 1.61 ± 0.11 | 11 |
| Δ3: …LVIFLDATYHLPPPD | 9.04 | 5.05 ± 0.08 | 1.46 ± 0.19 | 12 |
| Δ4: …LVIFLDATYHLPPP | 7.00 | 5.13 ± 0.15 | 1.75 ± 0.13 | 10 |
| Δ8: …LVIFLDATYH | 8.36 | 5.10 ± 0.16 | 1.79 ± 0.20 | 7 |
| Δ10: …LVIFLDAT | 11.6 | 4.94 ± 0.08b | 1.45 ± 0.21 | 9 |
| Δ13: …LVIFL | 15.0 | 4.84 ± 0.14b | 1.32 ± 0.30 | 11 |
| Δ15: …LVI | 4.25 | 5.33 ± 0.15b | 1.87 ± 0.20 | 9 |
| δ subunit | ||||
| WT: …WIFLQGVYNQPPPQPFPGDPYSYNVQDKRFI | 7.61 | 5.12 ± 0.07 | 1.70 ± 0.47 | 50 |
| Δ1: …WIFLQGVYNQPPPQPFPGDPYSYNVQDKRF | 9.20 | 5.04 ± 0.07 | 1.46 ± 0.20 | 8 |
| Δ2: …WIFLQGVYNQPPPQPFPGDPYSYNVQDKR | 7.72 | 5.13 ± 0.13 | 1.71 ± 0.13 | 8 |
| Δ3: …WIFLQGVYNQPPPQPFPGDPYSYNVQDK | 5.95 | 5.24 ± 0.14 | 1.55 ± 0.10 | 8 |
| Δ4: …WIFLQGVYNQPPPQPFPGDPYSYNVQD | 8.11 | 5.10 ± 0.07 | 1.60 ± 0.21 | 8 |
| Δ8: …WIFLQGVYNQPPPQPFPGDPYSY | 8.88 | 5.06 ± 0.07 | 1.50 ± 0.33 | 9 |
| Δ12: …WIFLQGVYNQPPPQPFPGD | 9.90 | 5.01 ± 0.06 | 1.32 ± 0.18 | 8 |
| Δ16: …WIFLQGVYNQPPPQP | 14.2 | 4.85 ± 0.07b | 1.68 ± 0.24 | 8 |
| Δ20: …WIFLQGVYNQP | 15.1 | 4.84 ± 0.12b | 1.51 ± 0.20 | 8 |
| Δ24: …WIFLQGV | 7.59 | 5.12 ± 0.01 | 1.55 ± 0.13 | 3 |
| Δ28: …WIF | No currentc | — | — | 8 |
| ε subunit | ||||
| WT: …SVGSSLIFLGAYFNRVPDLPYAPCIQP | 7.61 | 5.12 ± 0.07 | 1.70 ± 0.47 | 50 |
| Δ1: …SVGSSLIFLGAYFNRVPDLPYAPCIQ | 7.86 | 5.11 ± 0.05 | 1.62 ± 0.10 | 8 |
| Δ2: …SVGSSLIFLGAYFNRVPDLPYAPCI | 6.40 | 5.20 ± 0.05 | 1.72 ± 0.08 | 8 |
| Δ3: …SVGSSLIFLGAYFNRVPDLPYAPC | 8.44 | 5.08 ± 0.07 | 1.67 ± 0.11 | 9 |
| Δ4: …SVGSSLIFLGAYFNRVPDLPYAP | 9.26 | 5.04 ± 0.06 | 1.47 ± 0.17 | 8 |
| Δ8: …SVGSSLIFLGAYFNRVPDL | 6.20 | 5.22 ± 0.10 | 1.75 ± 0.25 | 8 |
| Δ13: …SVGSSLIFLGAYFN | 3.47 | 5.46 ± 0.05b | 1.87 ± 0.24 | 8 |
| Δ16: …SVGSSLIFLGA | 4.22 | 5.38 ± 0.06b | 1.87 ± 0.22 | 8 |
| Δ18: …SVGSSLIFL | 1.89 | 5.74 ± 0.13b | 1.99 ± 0.16 | 9 |
| Δ20: …SVGSSLI | 1.21 | 5.92 ± 0.09b | 1.87 ± 0.37 | 4 |
| Δ24: …SVG | No currentc | — | — | 8 |
a
Measurements performed 1 to 4 days after cRNA injection (Vhold ranging from −20 to −80 mV). Error values are represented as standard deviation.
b
p < 0.001 relative to WT via one-way ANOVA followed by Dunnet’s post hoc test.
c
No significant current observed up to 4 days after cRNA injection.