Table 2. Maximal fitted response and potency of ACh and NS9283 from concatenated α4β2 nAChRs
ConstructSubunitAChNS9283Both
EmaxpEC50_1pEC50_2FracnE31.6 µMEmaxpEC50nAChmax current
%%%nA
α4 (10:1)β2102 ± 15.7 ± 0.33.9 ± 0.040.11 ± 0.0314760 ± 70860 ± 605.3 ± 0.1138,100 ± 900 (27)
α4VFL (10:1)β2104 ± 25.0 ± 0.13.9 ± 0.30.71 ± 0.129−9.9 ± 1.8No pos. pot.N/A161,700 ± 300 (25)
Tetrameric
β-6-α-9-β-6-α109 ± 55.7 ± 0.23.8 ± 0.20.45 ± 0.076170 ± 20220 ± 305.0 ± 0.2649 ± 9 (12)
β-6-α-9-β-6-αα4100 ± 15.9 ± 0.83.8 ± 0.040.035 ± 0.02081,100 ± 1001,300 ± 1005.2 ± 0.161,500 ± 300 (14)
β-6-α-9-β-6-αα4VFL109 ± 45.0 ± 0.23.6 ± 0.20.41 ± 0.099130 ± 10170 ± 205.0 ± 0.25720 ± 130 (14)
β-6-α-9-β-6-α (1:5)α4VFL102 ± 25.5 ± 0.34.2 ± 0.20.32 ± 0.1313100 ± 10130 ± 205.1 ± 0.26850 ± 170 (19)
β-6-α-9-β-6-α (1:25)α4VFL106 ± 25.4 ± 0.14.0 ± 0.20.40 ± 0.129130 ± 10140 ± 105.4 ± 0.18310 ± 40 (15)
Pentameric
β-21a-α-β-α-α101 ± 15.9 ± 0.33.7 ± 0.020.060 ± 0.01112930 ± 301,100 ± 405.1 ± 0.1142,300 ± 400 (15)
β-21a-α-β-α-αVFL105 ± 15.2 ± 0.14.0 ± 0.20.59 ± 0.071441 ± 448 ± 55.3 ± 0.2192,400 ± 400 (22)
β-21a-α-α-β-α100 ± 26.1 ± 0.64.0 ± 0.050.060 ± 0.02514780 ± 90910 ± 705.3 ± 0.195,300 ± 700 (23)
β-21a-α-αVFL-β-α102 ± 25.3 ± 0.24.3 ± 0.20.46 ± 0.181955 ± 675 ± 95.0 ± 0.2232,000 ± 200 (39)
β-21a-αVFL-α-β-α104 ± 15.2 ± 0.14.1 ± 0.10.44 ± 0.11285 ± 10102 ± 105.2 ± 0.112600 ± 60 (12)
β-3a-α-β-α-α102 ± 16.0 ± 0.34.0 ± 0.040.11 ± 0.029640 ± 90800 ± 905.1 ± 0.25700 ± 120 (14)
β-3a-α-β-α-αVFL104 ± 15.4 ± 0.14.3 ± 0.10.53 ± 0.081411 ± 213 ± 1a5.8 ± 0.2151,400 ± 400 (29)
β-3a-αVFL-β-α-α105 ± 15.6 ± 0.14.1 ± 0.10.39 ± 0.0515200 ± 20240 ± 205.2 ± 0.19440 ± 80 (24)
β-3a-αVFL-α-β-α105 ± 45.1 ± 0.33.6 ± 0.20.28 ± 0.109270 ± 10340 ± 205.1 ± 0.112730 ± 120 (17)

Data for ACh and NS9283 obtained from tetrameric or pentameric concatenated constructs are handled and presented as described in Table 1. Longer incubation times of 3–7 d were generally utilized to increase expression levels. Data for α4 and β2 or α4VFL and β2 are from Table 1 for reference purposes. No pos. pot., no positive potentiation.

  • a No NS9283 efficacy observed in ∼50% of oocytes, resulting in poor fitting, as evidenced by the apparent increase in potency.