Figure 3. Dependence of Low [Ca²⁺]_e-activated Current (I_LCA) on the Carboxy-terminal Residues of NALCN.

(A) Schematic illustration of the location of the NALCN C-terminal mutants. The C-terminal sequences (from the rat isoform, accession # NP_705894) are shown (right). Non-conserved (red) and conserved (blue) amino acid substitutions in the chicken isoform (accession # XP_416967) are highlighted. Shadowed sequences indicate sequence non-essential to I_LCA (deleted in Δ1623-1699). (B) Representative ΔI_L-Na recordings from SH-SY5Y cells transfected with NALCN deletion mutants Δ1623-1699 (with amino acids 1623-1699 deleted), Δ1724-1732 and Δ1738. (C) Summary of potentiation of ΔI_L-Na by lowering [Ca²⁺]_e from 2 mM to 0.1 mM, defined as percentage of increase ([ΔI_L-Na in 0.1 mM Ca²⁺ - ΔI_L-Na in 2 mM Ca²⁺]/ΔI_L-Na in 2 mM Ca²⁺). Data from transfected NALCN^-/- and SH-SY5Y cells were pooled. Measurements from the 5 full-length NALCN-transfected neurons used in Figure 2F were also included for comparison. See Figure S3 for the averaged sizes of ΔI_L-Na in 2 mM and 0.1 mM Ca²⁺ -containing baths.