Fig. 2. Ca²⁺ channel gene variants typically have opposite effects on L5PC firing and SANC pacemaking.

a The membrane potential time courses in control cells and cells implemented with a CACNA1C variant (the first variant in Supplementary Table S2), see Fig. 1a. b The f–I curves and pacemaking rhythms of the modeled cells implemented with a Ca²⁺ channel or transporter variant, see Fig. 1b. Apart from the CACNA1I variants that show mixed effects, it can be seen that those variants that increase the pacemaking rhythm in SANCs, decrease the L5PC firing frequency, and vice versa. Variant effects on threshold currents in L5PCs are generally small