Table 2

Effects of NR1 and NR2B mutants in and around the M1, M3, and M4 regions on block by TB-3-4, memantine, and MK-801

	Mutant	TB-3-4		Memantine		MK-801
	Mutant	IC₅₀	Mutant/WT^2-a	K_d(0)	Mutant/WT^2-a	zδ	Mutant/WT^2-a	IC₅₀	Mutant/WT^2-a	K_d(0)	Mutant/WT^2-a	zδ	Mutant/WT^2-a	IC₅₀	Mutant/WT^2-a
		μM		μM				μM		μM				μM
	Wild-Type NR1/NR2B	0.20		8.8		1.38		0.46		7.1		0.89		0.002
Pre-M1	NR1(F558L)/NR2B	0.83	4	27	3	1.52	1.1	0.40	1	2.4	0.3	0.84	0.9	0.024	12
M1	NR1(W563L)/NR2B	2.1	10	52	6	1.30	0.9	0.52	1	3.9	1	0.74	0.8	0.037	19
	NR1(W563A)/NR2B	1.6	8	100	11	1.52	1.1	0.38	1	1.0	0.1	0.51	0.6	0.098	49
	NR1(W563Y)/NR2B	0.14	1	5.7	1	1.39	1.0	0.45	1	11	2	0.92	1.0	0.001	1
	NR1(W563F)/NR2B	0.15	1	7.8	1	1.47	1.1	0.46	1	6.7	1	0.87	1.0	0.003	2
M1	NR1/NR2B(W559L)	12	59	569	65	1.41	1.0	0.32	1	N.D.		N.D.		0.66	330
	NR1/NR2B(W559Y)	0.52	3	26	3	1.55	1.1	0.31	1	3.0	0.4	0.83	0.9	0.043	22
	NR1/NR2B(W559F)	2.7	13	174	20	1.59	1.2	0.36	1	2.1	0.3	0.69	0.8	0.059	30
M3	NR1(A645S)/NR2B	0.23	1	11	1	1.52	1.1	2.6	6	67	9	1.04	1.2	0.11	55
	NR1(A645T)/NR2B	0.61	3	34	4	1.57	1.1	0.56	1	12	2	1.01	1.1	0.079	40
M3	NR1(Y647L)/NR2B	0.05	0.3	N.D.		N.D.		2.1	4	10	1	1.01	1.1	0.005	3
	NR1(Y647A)/NR2B	0.22	1	33	4	1.77	1.3	0.20	0.4	0.9	0.1	0.50	0.6	0.027	14
	NR1(Y647F)/NR2B	0.08	0.4	3.6	0.4	1.35	1.0	1.0	2	23	3	0.87	1.0	0.005	3
	NR1(Y647W)/NR2B	0.21	1	11	1	1.39	1.0	0.88	2	8.4	1	0.86	1.0	0.006	3
M3	NR1/NR2B(Y646L)	1.9	9	50	6	1.34	1.0	0.47	1	6.2	1	0.75	0.8	0.022	11
M3	NR1(N650A)/NR2B	5.9	29	181	21	1.20	0.9	0.54	1	5.9	1	0.88	1.0	0.013	7
	NR1(N650D)/NR2B	0.02	0.1	1.2	0.1	1.69	1.2	0.56	1	21	3	0.99	1.1	0.013	7
	NR1(N650Q)/NR2B	0.53	3	35	4	1.41	1.0	0.45	1	7.4	1	0.99	1.1	0.004	2
	NR1/NR2B(N649Q)	5.7	28	298	34	1.31	0.9	0.45	1	4.1	1	0.90	1.0	0.022	11
M3	NR1(A652T)/NR2B	1.1	6	71	8	1.69	1.2	0.43	1	3.5	1	0.78	0.9	0.004	2
	NR1(A653T)/NR2B	0.10	1	4.5	1	1.46	1.1	1.7	4	61	9	1.20	1.3	0.010	5
	NR1(A653V)/NR2B	0.29	1	30	3	1.52	1.1	0.65	1	11	2	1.03	1.2	0.003	2
Post-M3	NR1(L655A)/NR2B	9.1	45	407	46	1.32	1.0	0.61	1	2.5	0.4	0.93	1.0	0.034	17
	NR1(L655V)/NR2B	1.56	8	52	6	1.45	1.1	0.65	1	8.6	1	1.01	1.1	0.003	2
Post-M3	NR1(V656A)/NR2B	0.05	0.3	4.3	1	1.61	1.2	1.77	4	64	9	1.08	1.2	0.003	2
Post-M3	NR1(E662Q)/NR2B	0.33	2	23	3	1.39	1.0	0.40	1	5.2	1	0.96	1.1	0.003	2
Post-M3	NR1(D669N)/NR2B	1.21	6	27	3	1.51	1.1	0.40	1	3.7	1	0.90	1.0	0.014	7
Post-M3	NR1/NR2B(D668N)	1.1	6	71	8	1.56	1.1	0.32	1	2.4	0.3	0.69	0.8	0.030	15
Pre-M4	NR1(T807C)/NR2B	7.3	36	969	110	1.70	1.2	0.45	1	2.2	0.3	0.66	0.7	0.030	15
	NR1(T807S)/NR2B	0.92	5	43	5	1.51	1.1	0.43	1	9.1	1	1.01	1.1	0.003	2
	NR1(T807V)/NR2B	0.11	1	6.4	1	1.64	1.2	0.51	1	10	1	1.05	1.2	0.003	2
Pre-M4	NR1(T809A)/NR2B	0.42	2	28	3	1.49	1.1	0.61	1	7.4	1	0.92	1.0	0.003	2
Pre-M4	NR1(T809S)/NR2B	0.15	1	15	2	1.48	1.1	0.49	1	11	2	0.93	1.0	0.003	2

Values of the IC₅₀ were determined from concentration-inhibition curves, and values of theK _d(0) and zδ were determined using voltage ramps analyzed with the Woodhull model of voltage-dependent block.

N.D., not determined.
↵2-a Ratio of the IC₅₀,K _d(0), or zδ for mutant/wild-type.