Table 1.

Kinetics, affinities and efficacies of ddKIIIA and analogs in blocking Na_V1.2^a

Peptide	kon	koff	Kd	IC50 (95% C.I.)	rINad
	µM−1•min−1	min−1	µM	µM	%
ddKIIIA	0.75 ± 0.015	0.01 ± 0.0015	0.013 ± 0.002	N.A.b	5 ± 1.1
ddKIIIA[K7A]	0.69 ± 0.11	0.13 ± 0.03	0.19 ± 0.05	0.21 (0.17 – 0.25)	24 ± 2.1
ddKIIIA[K7D]	0.08 ± 0.005	0.083 ± 0.02	1.04 ± 0.26	1 (0.85 – 1.2)	5 ± 2.4
ddKIIIA[K7S]	0.77 ± 0.07	0.11 ± 0.02	0.14 ± 0.03	0.31 (0.26 – 0.37)	29 ± 1.7
ddKIIIA[K7F]	0.55 ± 0.05	0.3 ± 0.04	0.55 ± 0.09	0.6 (0.52 – 0.7)	6 ± 2.0
ddKIIIA[K7G]	1.2 ± 0.1	0.67 ± 0.11	0.56 ± 0.1	0.47 (0.36 – 0.6)	29 ± 2.6
ddKIIIA[K7L]	0.39 ± 0.15	0.2 ± 0.009	0.51 ± 0.2	0.87 (0.76 – 1.0)	7 ± 1.7
ddKIIIA[K7V]	0.33 ± 0.018	0.091 ± 0.014	0.28 ± 0.045	0.34 (0.3 – 0.38)	14 ± 1.4
ddKIIIA[K7T]	0.1 ± 0.015	0.09 ± 0.006	0.9 ± 0.15	2.3 (1.8 – 3.0)	19 ± 3.3
ddKIIIA[K7dap]	1.2 ± 0.06	0.06 ± 0.008	0.05 ± 0.007	0.13 (0.09 – 0.19)	18 ± 1.3
KIIIAb	0.3 ± 0.03	0.0016 ± 0.0016	0.0053 ± 0.005	N.A.c	5 ± 3
KIIIA[K7A]b	0.13 ± 0.006	0.015 ± 0.005	0.115 ± 0.038	N.A.c	23 ± 1
KIIIA[K7D]	0.02 ± 0.002	0.008 ± 0.001	0.4 ± 0.06	N.A.c	6 ± 2.0

^aRate constants were determined as described under Materials and Methods. Steady-state IC₅₀ and rI_Na values were obtained with data and equation presented in Fig. 2. Standard deviation and 95% Confidence Intervals (95% C.I.) were calculated from at least three independent experiments using Prism software. For comparison, also shown are data for KIIIA and KIIIA[K7A] from ref. (18).

^bData from ref. (18).

^cIC₅₀ value was not obtained, because the rates of block using peptide concentrations in the range of the expected IC₅₀ were too slow to provide accurate steady-state levels of block within the time frame of the experiments.

^drI_Na for ddKIIIA, KIIIA, and KIIIA[K7A] were directly measured using a saturating peptide concentration, and those for the remaining peptides represent the plateaus of the best-fit curves as described in Fig. 2.