Biophysical classification of a CACNA1D de novo mutation as a high-risk mutation for a severe neurodevelopmental disorder

Table 2 Normalized inactivation kinetic parameters of mutation S652L

α₁-subunit	r₅₀	r₁₀₀	r₂₅₀	r₅₀₀	r₁₀₀₀	r₅₀₀₀	n
Remaining I_Ca [%]
WT_L	65.6 ± 2.66	54.5 ± 2.96	36.9 ± 2.96	24.9 ± 2.65	16.9 ± 2.40	8.60 ± 2.20	23
S652L_L	52.8 ± 2.05***	35.2 ± 1.92***	17.1 ± 1.68***	10.8 ± 1.52***	8.04 ± 1.43**	5.33 ± 1.33	22
WT_S	29.3 ± 2.07	23.3 ± 1.90	17.1 ± 1.71	12.9 ± 1.45	10.1 ± 1.10	6.21 ± 0.81	20
S652L_S	26.4 ± 1.47	17.6 ± 1.25*	10.5 ± 0.99**	7.11 ± 1.05**	6.15 ± 0.63**	3.34 ± 0.40**	22
Remaining I_Ba [%]
WT_L	92.55 ± 0.77	88.74 ± 1.02	79.10 ± 1.77	68.4 ± 2.75	57.37 ± 3.36	30.26 ± 3.30	17
S652L_L	86.78 ± 0.92***	76.91 ± 1.70***	59.05 ± 2.42***	47.17 ± 2.94***	36.33 ± 3.12***	17.24 ± 2.70**	14
WT_S	93.57 ± 0.88	88.24 ± 1.46	76.96 ± 2.83	64.48 ± 3.64	50.89 ± 4.26	25.67 ± 3.49	19
S652L_S	84.74 ± 1.66***	72.67 ± 2.70***	53.91 ± 3.35***	40.74 ± 3.35***	29.98 ± 2.76***	15.27 ± 1.92*	17

r values represent the percent of remaining I_Ca or I_Ba after 50, 100, 250, 500, 1000 and 5000 ms (5-s depolarization from a HP of − 89 mV to V_max). All values are presented as mean ± SEM (> 3 independent transfections). Statistics: unpaired Student’s t test of r values, *p < 0.05, **p < 0.01, ***p < 0.001 in comparison to respective WT. n, number of recordings; WT, wild-type

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