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. 2025 Jul 15;14:RP105696. doi: 10.7554/eLife.105696

Figure 2. Global Scn2a, Scn8a, or dual loss in compartmental models distinctly impacts key action potential (AP) properties.

(A) NaV1.6 and NaV1.2 are equally expressed in soma and proximal dendrites. Expression pattern is more distinct in other regions with NaV1.6 enriched in the distal axon initial segment (AIS), axon, and nodes of Ranvier, whereas NaV1.2 is found exclusively in the proximal AIS and distal dendrites. (B) Compartmental model representing changes to phase plots when NaV isoform expression is reduced from 100% (warmer colors) to 0% (in 10% increments) based on known localization across distinct neuronal localities. Lower NaV1.6 expression depolarized spike threshold and decreased both AIS and somatic AP velocity (dV/dt). Reduced NaV1.2 expression largely impacts backpropagation and somatic AP velocity. (C) Empirical observations of phase plot following near-complete channel block with ASCs. Darker trace represents phase plot taken at baseline prior to –12 mV hold for 30 s (see Figure 3A). Colored traces represent recovery phase plots at different times post –12 mV hold for 30 s with warmer colors depicting more time lapsed and increased channel recovery.

Figure 2.

Figure 2—figure supplement 1. Compartmental model sensitivity analysis.

Figure 2—figure supplement 1.

(A) To assess model sensitivity, NaV1.6 and NaV1.2 distribution is shifted throughout the axon initial segment (AIS). The AIS crossover point is adjusted from baseline with NaV1.6 extended into the proximal AIS (left 2) or NaV1.2 extended into the distal AIS (right 2 and 5). (B) Heat maps for action potential (AP) threshold and peak somatic dV/dt at different AIS crossover points. NaV1.2 and NaV1.6 ratios are also varied along the y-axis. (C) Example phase plane traces at different AIS crossover positions. Each AIS crossover position shows individual plots based on the different NaV ratios. Increased NaV1.2 density consistently depolarized AP threshold, while dV/dt peaks are randomly altered at the different density ratios. Scale bars are unique to each AIS crossover position.