Figure 3

Amplitude of the Na⁺-dependent component of the NALCN current carried out by the CLIFAHDD variants (Y578S, L509S) and the IHPRF variant (W1287L) of the NALCN channel. (A) Representative current traces elicited by a voltage ramp protocol (from −100 mV to +100 mV) in the presence (black traces) and in the absence (red traces) of extracellular Na⁺. (B) Representative current traces elicited by a voltage step protocol (HP 0 mV, test pulse (TP) at −40 mV) in the presence (black traces) and in the absence (red traces) of extracellular Na⁺. (C) Percentage of current inhibition obtained in Na⁺-free condition for mock-transfected cells (34.51 ± 18.37%, n = 14), for NALCN-transfected cells (64.41 ± 22.67%, n = 7), for NALCN-Y578S-transfected cells (87.81 ± 11.2%, n = 7), NALCN-L509S-transfected cells (84.25 ± 12.06%, n = 10) and for NALCN-W1287L-transfected cells (37.56 ± 12.06%, n = 5). Compared to the control condition, the percentage of inhibition was significantly larger for NALCN-wt (p = 0.026), NALCN-Y578S (p < 0.0001), NALCN-L509S (p < 0.0001) but not for NALCN-W1287L (p = 0.864). A significant difference in the percentage of inhibition was also found for NALCN-wt compared to its pathogenic variant Y578S (p = 0.017) but not for L509S (p = 0.157) and W1287L (p = 0.197). P values were calculated with a Mann-Whitney statistical test.