Table 2. Maximal fitted response and... | Rockefeller University Press

Table 2.

Maximal fitted response and potency of ACh and NS9283 from concatenated α4β2 nAChRs

Construct	Subunit	ACh					NS9283				Both
Construct	Subunit	E_max	pEC_{50_1}	pEC_{50_2}	Frac	n	E_{31.6 µM}	E_max	pEC₅₀	n	ACh_max current
		%					%	%			nA
α4 (10:1)	β2	102 ± 1	5.7 ± 0.3	3.9 ± 0.04	0.11 ± 0.03	14	760 ± 70	860 ± 60	5.3 ± 0.1	13	8,100 ± 900 (27)
α4^VFL (10:1)	β2	104 ± 2	5.0 ± 0.1	3.9 ± 0.3	0.71 ± 0.12	9	−9.9 ± 1.8	No pos. pot.	N/A	16	1,700 ± 300 (25)
Tetrameric
β-6-α-9-β-6-α		109 ± 5	5.7 ± 0.2	3.8 ± 0.2	0.45 ± 0.07	6	170 ± 20	220 ± 30	5.0 ± 0.2	6	49 ± 9 (12)
β-6-α-9-β-6-α	α4	100 ± 1	5.9 ± 0.8	3.8 ± 0.04	0.035 ± 0.020	8	1,100 ± 100	1,300 ± 100	5.2 ± 0.1	6	1,500 ± 300 (14)
β-6-α-9-β-6-α	α4^VFL	109 ± 4	5.0 ± 0.2	3.6 ± 0.2	0.41 ± 0.09	9	130 ± 10	170 ± 20	5.0 ± 0.2	5	720 ± 130 (14)
β-6-α-9-β-6-α (1:5)	α4^VFL	102 ± 2	5.5 ± 0.3	4.2 ± 0.2	0.32 ± 0.13	13	100 ± 10	130 ± 20	5.1 ± 0.2	6	850 ± 170 (19)
β-6-α-9-β-6-α (1:25)	α4^VFL	106 ± 2	5.4 ± 0.1	4.0 ± 0.2	0.40 ± 0.12	9	130 ± 10	140 ± 10	5.4 ± 0.1	8	310 ± 40 (15)
Pentameric
β-21a-α-β-α-α		101 ± 1	5.9 ± 0.3	3.7 ± 0.02	0.060 ± 0.011	12	930 ± 30	1,100 ± 40	5.1 ± 0.1	14	2,300 ± 400 (15)
β-21a-α-β-α-α^VFL		105 ± 1	5.2 ± 0.1	4.0 ± 0.2	0.59 ± 0.07	14	41 ± 4	48 ± 5	5.3 ± 0.2	19	2,400 ± 400 (22)
β-21a-α-α-β-α		100 ± 2	6.1 ± 0.6	4.0 ± 0.05	0.060 ± 0.025	14	780 ± 90	910 ± 70	5.3 ± 0.1	9	5,300 ± 700 (23)
β-21a-α-α^VFL-β-α		102 ± 2	5.3 ± 0.2	4.3 ± 0.2	0.46 ± 0.18	19	55 ± 6	75 ± 9	5.0 ± 0.2	23	2,000 ± 200 (39)
β-21a-α^VFL-α-β-α		104 ± 1	5.2 ± 0.1	4.1 ± 0.1	0.44 ± 0.1	12	85 ± 10	102 ± 10	5.2 ± 0.1	12	600 ± 60 (12)
β-3a-α-β-α-α		102 ± 1	6.0 ± 0.3	4.0 ± 0.04	0.11 ± 0.02	9	640 ± 90	800 ± 90	5.1 ± 0.2	5	700 ± 120 (14)
β-3a-α-β-α-α^VFL		104 ± 1	5.4 ± 0.1	4.3 ± 0.1	0.53 ± 0.08	14	11 ± 2	13 ± 1^{^a}	5.8 ± 0.2	15	1,400 ± 400 (29)
β-3a-α^VFL-β-α-α		105 ± 1	5.6 ± 0.1	4.1 ± 0.1	0.39 ± 0.05	15	200 ± 20	240 ± 20	5.2 ± 0.1	9	440 ± 80 (24)
β-3a-α^VFL-α-β-α		105 ± 4	5.1 ± 0.3	3.6 ± 0.2	0.28 ± 0.10	9	270 ± 10	340 ± 20	5.1 ± 0.1	12	730 ± 120 (17)

Construct	Subunit	ACh					NS9283				Both
Construct	Subunit	E_max	pEC_{50_1}	pEC_{50_2}	Frac	n	E_{31.6 µM}	E_max	pEC₅₀	n	ACh_max current
		%					%	%			nA
α4 (10:1)	β2	102 ± 1	5.7 ± 0.3	3.9 ± 0.04	0.11 ± 0.03	14	760 ± 70	860 ± 60	5.3 ± 0.1	13	8,100 ± 900 (27)
α4^VFL (10:1)	β2	104 ± 2	5.0 ± 0.1	3.9 ± 0.3	0.71 ± 0.12	9	−9.9 ± 1.8	No pos. pot.	N/A	16	1,700 ± 300 (25)
Tetrameric
β-6-α-9-β-6-α		109 ± 5	5.7 ± 0.2	3.8 ± 0.2	0.45 ± 0.07	6	170 ± 20	220 ± 30	5.0 ± 0.2	6	49 ± 9 (12)
β-6-α-9-β-6-α	α4	100 ± 1	5.9 ± 0.8	3.8 ± 0.04	0.035 ± 0.020	8	1,100 ± 100	1,300 ± 100	5.2 ± 0.1	6	1,500 ± 300 (14)
β-6-α-9-β-6-α	α4^VFL	109 ± 4	5.0 ± 0.2	3.6 ± 0.2	0.41 ± 0.09	9	130 ± 10	170 ± 20	5.0 ± 0.2	5	720 ± 130 (14)
β-6-α-9-β-6-α (1:5)	α4^VFL	102 ± 2	5.5 ± 0.3	4.2 ± 0.2	0.32 ± 0.13	13	100 ± 10	130 ± 20	5.1 ± 0.2	6	850 ± 170 (19)
β-6-α-9-β-6-α (1:25)	α4^VFL	106 ± 2	5.4 ± 0.1	4.0 ± 0.2	0.40 ± 0.12	9	130 ± 10	140 ± 10	5.4 ± 0.1	8	310 ± 40 (15)
Pentameric
β-21a-α-β-α-α		101 ± 1	5.9 ± 0.3	3.7 ± 0.02	0.060 ± 0.011	12	930 ± 30	1,100 ± 40	5.1 ± 0.1	14	2,300 ± 400 (15)
β-21a-α-β-α-α^VFL		105 ± 1	5.2 ± 0.1	4.0 ± 0.2	0.59 ± 0.07	14	41 ± 4	48 ± 5	5.3 ± 0.2	19	2,400 ± 400 (22)
β-21a-α-α-β-α		100 ± 2	6.1 ± 0.6	4.0 ± 0.05	0.060 ± 0.025	14	780 ± 90	910 ± 70	5.3 ± 0.1	9	5,300 ± 700 (23)
β-21a-α-α^VFL-β-α		102 ± 2	5.3 ± 0.2	4.3 ± 0.2	0.46 ± 0.18	19	55 ± 6	75 ± 9	5.0 ± 0.2	23	2,000 ± 200 (39)
β-21a-α^VFL-α-β-α		104 ± 1	5.2 ± 0.1	4.1 ± 0.1	0.44 ± 0.1	12	85 ± 10	102 ± 10	5.2 ± 0.1	12	600 ± 60 (12)
β-3a-α-β-α-α		102 ± 1	6.0 ± 0.3	4.0 ± 0.04	0.11 ± 0.02	9	640 ± 90	800 ± 90	5.1 ± 0.2	5	700 ± 120 (14)
β-3a-α-β-α-α^VFL		104 ± 1	5.4 ± 0.1	4.3 ± 0.1	0.53 ± 0.08	14	11 ± 2	13 ± 1^{^a}	5.8 ± 0.2	15	1,400 ± 400 (29)
β-3a-α^VFL-β-α-α		105 ± 1	5.6 ± 0.1	4.1 ± 0.1	0.39 ± 0.05	15	200 ± 20	240 ± 20	5.2 ± 0.1	9	440 ± 80 (24)
β-3a-α^VFL-α-β-α		105 ± 4	5.1 ± 0.3	3.6 ± 0.2	0.28 ± 0.10	9	270 ± 10	340 ± 20	5.1 ± 0.1	12	730 ± 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 α4^VFL and β2 are from Table 1 for reference purposes. No pos. pot., no positive potentiation.

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

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