TABLE 1.

The effects of M4 Ala mutations on the function of GLIC and ELIC

Dose-responsea
GLIC				ELIC
Mutant	pH50	Hill slope	n	Mutant	EC50	Hill slope	n
					mm
WT	5.03 ± 0.08	1.42 ± 0.49	38	WT	0.93 ± 0.13	2.13 ± 0.36	23
F317A	5.41 ± 0.08b	1.31 ± 0.30	8	L321A	0.58 ± 0.08b	2.99 ± 0.31	10
G316A	5.01 ± 0.08	1.74 ± 0.48	8	T320A	0.59 ± 0.06b	2.53 ± 0.73	8
F315A	4.69 ± 0.01b,c	1.71 ± 0.07	8	I319A	0.86 ± 0.16	2.20 ± 0.38	11
F314A	4.48 ± 0.02b,c	1.61 ± 0.11	10	G318A	0.76 ± 0.13b	2.13 ± 0.16	10
L313A	4.78 ± 0.05b	1.14 ± 0.13	6	R317A	0.55 ± 0.11b	2.41 ± 0.32	10
F312A	4.50 ± 0.01b	1.84 ± 0.04	6	I316A	0.63 ± 0.10b	2.52 ± 0.27	10
Ala-311	—	—	—	V315A	0.60 ± 0.08b	2.54 ± 0.14	9
L310A	4.47 ± 0.02b	1.57 ± 0.11	6	L314A	0.42 ± 0.05b	2.60 ± 0.36	8
I309A	5.05 ± 0.05	1.59 ± 0.24	7	V313A	0.95 ± 0.12	2.58 ± 0.41	10
I308A	5.08 ± 0.02	1.55 ± 0.09	6	C312A	0.55 ± 0.08b	2.11 ± 0.26	10
N307A	4.42 ± 0.01b	2.43 ± 0.13	10	G311A	0.51 ± 0.10b	2.02 ± 0.20	11
Ala-306	—	—	—	I310A	0.88 ± 0.09	1.99 ± 0.11	10
L305A	5.11 ± 0.09d	1.53 ± 0.41	9	Ala-309	—	—	—
L304A	5.08 ± 0.13	1.57 ± 0.74	7	L308A	0.52 ± 0.08b	2.76 ± 0.53	8
F303A	4.48 ± 0.09b	1.85 ± 0.65	8	F307A	0.57 ± 0.09b	2.48 ± 0.24	8
V302A	4.81 ± 0.04b	1.64 ± 0.27	7	G306A	0.97 ± 0.10	2.23 ± 0.23	8
V301A	4.92 ± 0.06e	1.51 ± 0.35	8	L305A	0.57 ± 0.04b	2.36 ± 0.40	8
P300A	NCf	NC	8	P304A	—g	—g	10
F299A	5.04 ± 0.09	1.44 ± 0.38	6	F303A	0.19 ± 0.07b	2.03 ± 0.40	10
Ala-298	—	—	—	Ala-302	—	—	—
I297A	4.99 ± 0.08	1.20 ± 0.26	6	L301A	0.40 ± 0.07b	2.03 ± 0.34	9
R296A	4.65 ± 0.03b	1.61 ± 0.13	9	R300A	0.40 ± 0.05b	2.54 ± 0.37	11
S295A	5.12 ± 0.1	1.36 ± 0.39	6	C299A	0.56 ± 0.09b	2.50 ± 0.18	9
Ala-294	—	—	—	R298A	0.58 ± 0.21b	2.09 ± 0.22	8
R293A	4.90 ± 0.12b	1.32 ± 0.49	8	Q297A	0.56 ± 0.09b	2.90 ± 0.43	7
T292A	4.86 ± 0.05b	1.69 ± 0.32	6	I296A	0.27 ± 0.03b	2.80 ± 0.45	10
I291A	4.78 ± 0.05b	1.15 ± 0.15	7	L295A	0.50 ± 0.11b	2.26 ± 0.28	8
S290A	4.89 ± 0.06b	1.53 ± 0.30	7	L294A	0.69 ± 0.17b	2.20 ± 0.13	8
Ala-289	—	—	—	D293A	0.46 ± 0.21b	2.13 ± 0.30	8
Ala-288	—	—	—	D292A	0.38 ± 0.07b	2.18 ± 0.20	9
R287A	4.93 ± 0.03d	1.50 ± 0.14	6	E291A	0.41 ± 0.06b	2.66 ± 0.48	11
Ala-286	—	—	—	V290A	0.53 ± 0.10b	2.00 ± 0.13	6
P285A	4.96 ± 0.07	1.47 ± 0.31	6	G289A	0.57 ± 0.03b	2.15 ± 0.11	6

^a Measurements performed 1–4 days after cRNA injection (V_hold ranging from −10 to −60 mV). Error values represent standard deviation.

^b p < 0.001 relative to WT ELIC/GLIC via one-way ANOVA followed by Dunnet's post hoc test.

^c Data from Ref. 39.

^d p < 0.05 relative to WT GLIC via one-way ANOVA followed by Dunnet's post hoc test.

^e p < 0.01 relative to WT GLIC via one-way ANOVA followed by Dunnet's post hoc test.

^f No significant current observed up to 4 days after cRNA injection.

^g Functionally distinct, traditional EC₅₀ values were not obtained.