Table 1. Equilibrium parameters for... | Rockefeller University Press

Table 1.

Equilibrium parameters for wild-type and mutant sodium channels

Mutation	Location	V_0.5	Slope factor	ΔΔG^o	h_0.5	Slope factor
		mV		kcal/mol	mV
hNa_V1.4		18.3 ± 1.2	1.39 ± 0.03		−65.8 ± 1.1	4.24 ± 0.12
ENC
S151K	Domain I S1	23.2 ± 0.8^b	1.37 ± 0.06	0.6	−66.5 ± 0.7	4.67 ± 0.06^b
D152R	Domain I S1	23.2 ± 0.9^b	1.37 ± 0.03	0.6	−64.1 ± 0.6	4.11 ± 0.25
E161R	Domain I S2	23.8 ± 1.0^c	1.57 ± 0.03^d	1.1	−60.5 ± 0.6^c	3.82 ± 0.08^b
E598K	Domain II S1	36.3 ± 0.9^d	1.59 ± 0.05^b	3.0	−59.8 ± 1.4^b	2.90 ± 0.14^d
N614K	Domain II S2	30.3 ± 0.8^d	1.52 ± 0.03^b	1.9	−61.0 ± 0.6^d	3.84 ± 0.20
E1051R	Domain III S1	26.0 ± 0.7^d	1.60 ± 0.02^d	1.5	−48.4 ± 1.2^d	3.16 ± 0.16^d
E1051D	Domain III S1	25.7 ± 1.3^d	1.39 ± 0.03	1.0	−62.1 ± 1.2^a	3.98 ± 0.15
D1069K	Domain III S2	30.0 ± 0.8^d	1.61 ± 0.04^c	2.1	−49.3 ± 1.9^d	3.56 ± 0.13^c
D1069E	Domain III S2	19.2 ± 1.2	1.43 ± 0.02	0.2	−64.4 ± 0.7	2.88 ± 0.11^d
E1373K	Domain IV S1	15.2 ± 1.0	1.73 ± 0.03^d	0.1	−50.3 ± 0.7^d	2.47 ± 0.07^d
E1373N	Domain IV S1	18.1 ± 1.2	1.60 ± 0.02^d	0.3	−49.9 ± 0.9^d	2.41 ± 0.06^d
E1373D	Domain IV S1	20.4 ± 0.9^a	1.39 ± 0.02	0.3	−65.8 ± 0.7	2.81 ± 0.07^d
N1389K	Domain IV S2	18.6 ± 1.1	1.65 ± 0.03^d	0.5	−48.7 ± 0.9^d	2.58 ± 0.12^d
N1389E	Domain IV S2	21.8 ± 1.0^a	1.31 ± 0.01^b	0.3	−71.5 ± 1.0^c	4.59 ± 0.11^a
N1389D	Domain IV S2	19.2 ± 0.7	1.33 ± 0.02	0.0	−75.4 ± 0.6^d	2.66 ± 0.03^d
HCR
N144K	Domain I S1	35.4 ± 1.2^d	1.58 ± 0.07^a	2.8	−61.7 ± 0.9^b	3.69 ± 0.70^b
N144R	Domain I S1	34.2 ± 1.2^d	1.40 ± 0.03	2.1	−62.3 ± 0.5^b	4.06 ± 0.09
N144D	Domain I S1	20.2 ± 0.7	1.19 ± 0.01^d	−0.1	−72.0 ± 0.5^d	5.13 ± 0.09^d
N144E	Domain I S1	20.1 ± 0.9	1.29 ± 0.02^b	0.1	−67.7 ± 0.3	5.06 ± 0.09^d
N591K	Domain II S1	34.3 ± 1.7^d	1.30 ± 0.03^a	1.8	−58.5 ± 1.0^d	2.89 ± 0.13^d
N591R	Domain II S1	34.4 ± 1.1^d	1.38 ± 0.03	2.0	−61.0 ± 0.4^c	5.93 ± 0.15^d
N591D	Domain II S1	32.0 ± 1.1^d	1.50 ± 0.04^a	2.1	−61.2 ± 0.4^c	4.54 ± 0.07^a
N591E	Domain II S1	18.8 ± 1.3	1.42 ± 0.02	0.1	−63.8 ± 0.7	4.52 ± 0.11
S1044K	Domain III S1	23.6 ± 0.8^c	1.43 ± 0.03	0.8	−57.9 ± 0.6^d	4.00 ± 0.13
S1044R	Domain III S1	30.4 ± 0.7^d	1.42 ± 0.02	1.6	−49.8 ± 0.6^d	4.22 ± 0.10
S1044N	Domain III S1	22.8 ± 0.6^b	1.39 ± 0.02	0.6	−60.6 ± 0.6^c	4.55 ± 0.07^a
S1044D	Domain III S1	21.4 ± 1.2	1.32 ± 0.02^a	0.2	−70.9 ± 0.5^c	3.99 ± 0.09
N1366K	Domain IV S1	19.3 ± 1.6	1.41 ± 0.02	0.2	−64.2 ± 1.2	3.88 ± 0.08^a
N1366R	Domain IV S1	21.5 ± 1.4	1.51 ± 0.11^c	0.7	−58.3 ± 0.8^d	2.64 ± 0.04^d
N1366D	Domain IV S1	26.3 ± 1.7^c	1.25 ± 0.04^b	0.7	−85.8 ± 0.6^d	3.37 ± 0.09^d
N1366E	Domain IV S1	21.8 ± 1.0^a	1.41 ± 0.02	0.5	−71.2 ± 1.3^b	3.44 ± 0.08^d
INC
E171R	Domain I S2	36.7 ± 2.1^d	1.24 ± 0.05^b	1.9	−75.7 ± 1.7^d	3.79 ± 0.25
K175E	Domain I S2	22.1 ± 1.2^b	1.37 ± 0.02^a	0.5	−65.0 ± 0.9	4.24 ± 0.14
N194K	Domain I S3	19.1 ± 1.0	1.33 ± 0.02	0.0	−68.7 ± 0.8^a	2.88 ± 0.04^d
D197R	Domain I S3	35.1 ± 1.5^d	1.28 ± 0.04^b	1.8	−76.1 ± 1.1^d	4.44 ± 0.24
E624K	Domain II S2	26.5 ± 1.2^d	1.44 ± 0.03	1.2	−63.7 ± 0.7	5.13 ± 0.14^d
K628E	Domain II S2	18.3 ± 0.9	1.34 ± 0.02^c	−0.1	−68.9 ± 0.9^a	3.95 ± 0.11
N643K	Domain II S3	17.7 ± 0.4	1.41 ± 0.02	0.0	−61.2 ± 0.8^b	4.51 ± 0.08
D646K	Domain II S3	27.6 ± 1.2^d	1.41 ± 0.03	1.2	−64.2 ± 0.6	3.95 ± 0.13
E1079R	Domain III S2	21.6 ± 0.9^a	1.57 ± 0.05^b	0.8	−63.4 ± 1.1	3.86 ± 0.16
K1083E	Domain III S2	20.7 ± 1.0^a	1.39 ± 0.02	0.3	−68.9 ± 0.7^b	3.71 ± 0.11^a
C1098K	Domain III S3	23.1 ± 1.0^b	1.27 ± 0.02^c	0.4	−75.7 ± 0.6^d	3.03 ± 0.11^d
D1101V	Domain III S3	20.2 ± 1.3	1.44 ± 0.02	0.3	−63.4 ± 1.0	4.54 ± 0.10
E1399K	Domain IV S2	20.2 ± 0.8	1.47 ± 0.02^a	0.4	−61.0 ± 0.9^b	3.29 ± 0.08^d
K1403E	Domain IV S2	20.7 ± 1.6	1.50 ± 0.04	0.5	−63.9 ± 1.0	3.03 ± 0.11^d
N1417K	Domain IV S3	24.2 ± 0.9^c	1.38 ± 0.01	0.7	−69.4 ± 0.6^b	3.77 ± 0.06^b
D1420K	Domain IV S3	22.4 ± 1.2^a	1.57 ± 0.04^c	0.9	−70.1 ± 0.8^b	2.83 ± 0.09^d

Mutation	Location	V_0.5	Slope factor	ΔΔG^o	h_0.5	Slope factor
		mV		kcal/mol	mV
hNa_V1.4		18.3 ± 1.2	1.39 ± 0.03		−65.8 ± 1.1	4.24 ± 0.12
ENC
S151K	Domain I S1	23.2 ± 0.8^b	1.37 ± 0.06	0.6	−66.5 ± 0.7	4.67 ± 0.06^b
D152R	Domain I S1	23.2 ± 0.9^b	1.37 ± 0.03	0.6	−64.1 ± 0.6	4.11 ± 0.25
E161R	Domain I S2	23.8 ± 1.0^c	1.57 ± 0.03^d	1.1	−60.5 ± 0.6^c	3.82 ± 0.08^b
E598K	Domain II S1	36.3 ± 0.9^d	1.59 ± 0.05^b	3.0	−59.8 ± 1.4^b	2.90 ± 0.14^d
N614K	Domain II S2	30.3 ± 0.8^d	1.52 ± 0.03^b	1.9	−61.0 ± 0.6^d	3.84 ± 0.20
E1051R	Domain III S1	26.0 ± 0.7^d	1.60 ± 0.02^d	1.5	−48.4 ± 1.2^d	3.16 ± 0.16^d
E1051D	Domain III S1	25.7 ± 1.3^d	1.39 ± 0.03	1.0	−62.1 ± 1.2^a	3.98 ± 0.15
D1069K	Domain III S2	30.0 ± 0.8^d	1.61 ± 0.04^c	2.1	−49.3 ± 1.9^d	3.56 ± 0.13^c
D1069E	Domain III S2	19.2 ± 1.2	1.43 ± 0.02	0.2	−64.4 ± 0.7	2.88 ± 0.11^d
E1373K	Domain IV S1	15.2 ± 1.0	1.73 ± 0.03^d	0.1	−50.3 ± 0.7^d	2.47 ± 0.07^d
E1373N	Domain IV S1	18.1 ± 1.2	1.60 ± 0.02^d	0.3	−49.9 ± 0.9^d	2.41 ± 0.06^d
E1373D	Domain IV S1	20.4 ± 0.9^a	1.39 ± 0.02	0.3	−65.8 ± 0.7	2.81 ± 0.07^d
N1389K	Domain IV S2	18.6 ± 1.1	1.65 ± 0.03^d	0.5	−48.7 ± 0.9^d	2.58 ± 0.12^d
N1389E	Domain IV S2	21.8 ± 1.0^a	1.31 ± 0.01^b	0.3	−71.5 ± 1.0^c	4.59 ± 0.11^a
N1389D	Domain IV S2	19.2 ± 0.7	1.33 ± 0.02	0.0	−75.4 ± 0.6^d	2.66 ± 0.03^d
HCR
N144K	Domain I S1	35.4 ± 1.2^d	1.58 ± 0.07^a	2.8	−61.7 ± 0.9^b	3.69 ± 0.70^b
N144R	Domain I S1	34.2 ± 1.2^d	1.40 ± 0.03	2.1	−62.3 ± 0.5^b	4.06 ± 0.09
N144D	Domain I S1	20.2 ± 0.7	1.19 ± 0.01^d	−0.1	−72.0 ± 0.5^d	5.13 ± 0.09^d
N144E	Domain I S1	20.1 ± 0.9	1.29 ± 0.02^b	0.1	−67.7 ± 0.3	5.06 ± 0.09^d
N591K	Domain II S1	34.3 ± 1.7^d	1.30 ± 0.03^a	1.8	−58.5 ± 1.0^d	2.89 ± 0.13^d
N591R	Domain II S1	34.4 ± 1.1^d	1.38 ± 0.03	2.0	−61.0 ± 0.4^c	5.93 ± 0.15^d
N591D	Domain II S1	32.0 ± 1.1^d	1.50 ± 0.04^a	2.1	−61.2 ± 0.4^c	4.54 ± 0.07^a
N591E	Domain II S1	18.8 ± 1.3	1.42 ± 0.02	0.1	−63.8 ± 0.7	4.52 ± 0.11
S1044K	Domain III S1	23.6 ± 0.8^c	1.43 ± 0.03	0.8	−57.9 ± 0.6^d	4.00 ± 0.13
S1044R	Domain III S1	30.4 ± 0.7^d	1.42 ± 0.02	1.6	−49.8 ± 0.6^d	4.22 ± 0.10
S1044N	Domain III S1	22.8 ± 0.6^b	1.39 ± 0.02	0.6	−60.6 ± 0.6^c	4.55 ± 0.07^a
S1044D	Domain III S1	21.4 ± 1.2	1.32 ± 0.02^a	0.2	−70.9 ± 0.5^c	3.99 ± 0.09
N1366K	Domain IV S1	19.3 ± 1.6	1.41 ± 0.02	0.2	−64.2 ± 1.2	3.88 ± 0.08^a
N1366R	Domain IV S1	21.5 ± 1.4	1.51 ± 0.11^c	0.7	−58.3 ± 0.8^d	2.64 ± 0.04^d
N1366D	Domain IV S1	26.3 ± 1.7^c	1.25 ± 0.04^b	0.7	−85.8 ± 0.6^d	3.37 ± 0.09^d
N1366E	Domain IV S1	21.8 ± 1.0^a	1.41 ± 0.02	0.5	−71.2 ± 1.3^b	3.44 ± 0.08^d
INC
E171R	Domain I S2	36.7 ± 2.1^d	1.24 ± 0.05^b	1.9	−75.7 ± 1.7^d	3.79 ± 0.25
K175E	Domain I S2	22.1 ± 1.2^b	1.37 ± 0.02^a	0.5	−65.0 ± 0.9	4.24 ± 0.14
N194K	Domain I S3	19.1 ± 1.0	1.33 ± 0.02	0.0	−68.7 ± 0.8^a	2.88 ± 0.04^d
D197R	Domain I S3	35.1 ± 1.5^d	1.28 ± 0.04^b	1.8	−76.1 ± 1.1^d	4.44 ± 0.24
E624K	Domain II S2	26.5 ± 1.2^d	1.44 ± 0.03	1.2	−63.7 ± 0.7	5.13 ± 0.14^d
K628E	Domain II S2	18.3 ± 0.9	1.34 ± 0.02^c	−0.1	−68.9 ± 0.9^a	3.95 ± 0.11
N643K	Domain II S3	17.7 ± 0.4	1.41 ± 0.02	0.0	−61.2 ± 0.8^b	4.51 ± 0.08
D646K	Domain II S3	27.6 ± 1.2^d	1.41 ± 0.03	1.2	−64.2 ± 0.6	3.95 ± 0.13
E1079R	Domain III S2	21.6 ± 0.9^a	1.57 ± 0.05^b	0.8	−63.4 ± 1.1	3.86 ± 0.16
K1083E	Domain III S2	20.7 ± 1.0^a	1.39 ± 0.02	0.3	−68.9 ± 0.7^b	3.71 ± 0.11^a
C1098K	Domain III S3	23.1 ± 1.0^b	1.27 ± 0.02^c	0.4	−75.7 ± 0.6^d	3.03 ± 0.11^d
D1101V	Domain III S3	20.2 ± 1.3	1.44 ± 0.02	0.3	−63.4 ± 1.0	4.54 ± 0.10
E1399K	Domain IV S2	20.2 ± 0.8	1.47 ± 0.02^a	0.4	−61.0 ± 0.9^b	3.29 ± 0.08^d
K1403E	Domain IV S2	20.7 ± 1.6	1.50 ± 0.04	0.5	−63.9 ± 1.0	3.03 ± 0.11^d
N1417K	Domain IV S3	24.2 ± 0.9^c	1.38 ± 0.01	0.7	−69.4 ± 0.6^b	3.77 ± 0.06^b
D1420K	Domain IV S3	22.4 ± 1.2^a	1.57 ± 0.04^c	0.9	−70.1 ± 0.8^b	2.83 ± 0.09^d

Mean values ± SEM from Boltzmann fits of I/V relations in 10–24 experiments. The free energy change in wild-type and mutant channels is calculated from 4zFV_0.5. The change in free energy of activation produced by mutation is given as ΔΔG⁰.

P ≤ 0.05.

P ≤ 0.01.

P ≤ 0.001.

P ≤ 0.0001.

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