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	Figure 1. Effects of CgNa on cloned mammalian NaV channel subtypes NaV1. 2–NaV1.8/β1 expressed in Xenopus oocytes. The tested mammalian isoforms originate from rat (r), human (h), or mouse (m). Left-hand panels show representative whole-cell current traces in control (black traces) and in presence of 10 μM CgNa (gray traces). Middle panels show normalized current–voltage relationships (n = 3–7) in control (●) and in presence of 10 μM CgNa (○). Right-hand panels show steady-state activation and inactivation curves (n = 3–7) in control (● and ■, respectively) and in presence of 10 μM CgNa (○ and □, respectively), fit with the Boltzmann equation.
	Figure 2. Effects of CgNa on the cloned insect NaV channel DmNaV1/tipE expressed in Xenopus oocytes. (A,B) Left-hand panels show representative whole-cell current traces in control (black traces) and in presence CgNa (gray traces) at a concentration of 100 nM (A) and 10 μM (B); middle panels show normalized current–voltage relationships (n = 3–6) in control (●) and in presence of CgNa (○) at a concentration of 100 nM (A) and 10 μM (B); right-hand panels display steady-state activation and inactivation curves (n = 3–6) in control (● and ■, respectively) and in presence of CgNa (○ and □, respectively) at a concentration of 100 nM (A) and 10 μM (B). (C) Time course of the increase (n = 6) in peak INa (Δ, 100 nM; ▲, 10 μM) and sustained INa measured after 100 ms (○, 100 nM; ●, 10 μM). (D) Dose–response curves displaying the concentration dependence of the CgNa-induced increase in INa peak (●) and sustained INa measured after 100 ms (▲). (E) Recovery from inactivation (n = 7) in control (●) and in the presence of 100 nM CgNa (○).
	Figure 3. Dose–response relationships of the effects of CgNa on the insect and mammalian NaV channels. Dose–response curves are constructed using the following three parameters to quantify the effects induced by CgNa: increase in peak INa (A), increase in INa 5 ms (B), and increase in INa 100 ms (C). Left-hand graphs show phyla-selectivity between insect and mammalian NaV channels, while right-hand graphs zoom in to show the subtype-selectivity among the mammalian NaV subtypes. (D,E) Bar diagram illustrating the differences in potency and efficacy of CgNa on the variety of assayed insect and mammalian NaV channels.
	Figure 4. Sequence alignment of IVS3–S4 from insect and mammalian NaV subtypes. Amino acid alignment of the transmembrane segments S3 and S4 from the homologous repeat DIV connected by the extracellular loop. The two sequences on top are from insect channels (MdNaV1 and DmNaV1; Md, house fly; Dm, fruit fly), the other sequences are from mammalian channel subtypes (NaV1.1–NaV1.9; r, rat; m, mouse; h, human). The NaV channel subtypes affected by CgNa are shown on a gray background, residues that differ to those in the sequence of NaV1.1–NaV1.3 are colored red. Amino acid residues discussed in the text are printed in bold. Positions of the outermost N-terminal residues in the aligned sequence of each subtype are: MdNaV1, 1668 (Uniprot accession number Q94615); DmNaV1, 1680 (P35500); rNaV1.1, 1602 (P04774); rNaV1.2, 1592 (P04775); rNaV1.3, 1538 (P08104); rNaV1.4, 1407 (P15390); hNaV1.5, 1589 (Q14524); mNaV1.6, 1581 (Q9WTU3); rNaV1.7, 1574 (O08562); rNaV1.8, 1538 (Q62968); rNaV1.9, 1407 (O88457).

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