Billen B , Debaveye S , Béress L , Garateix A , Tytgat J .

	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).

Armstrong, Sodium channels and gating currents. 1981, Pubmed

Armstrong, Sodium channels and gating currents. 1981, Pubmed
Ashcroft, From molecule to malady. 2006, Pubmed
Benzinger, A specific interaction between the cardiac sodium channel and site-3 toxin anthopleurin B. 1998, Pubmed
Black, Spinal sensory neurons express multiple sodium channel alpha-subunit mRNAs. 1996, Pubmed
Black, Changes in the expression of tetrodotoxin-sensitive sodium channels within dorsal root ganglia neurons in inflammatory pain. 2004, Pubmed
Bosmans, Deconstructing voltage sensor function and pharmacology in sodium channels. 2008, Pubmed , Xenbase
Bosmans, The sea anemone Bunodosoma granulifera contains surprisingly efficacious and potent insect-selective toxins. 2002, Pubmed , Xenbase
Bosmans, The poison Dart frog's batrachotoxin modulates Nav1.8. 2004, Pubmed , Xenbase
Cannon, Voltage-sensor mutations in channelopathies of skeletal muscle. 2010, Pubmed
Catterall, Inherited neuronal ion channelopathies: new windows on complex neurological diseases. 2008, Pubmed
Catterall, Sea anemone toxin and scorpion toxin share a common receptor site associated with the action potential sodium ionophore. 1978, Pubmed
Catterall, Neurotoxins as allosteric modifiers of voltage-sensitive sodium channels. 1979, Pubmed
Catterall, From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. 2000, Pubmed
Chahine, Sodium channel mutations in paramyotonia congenita uncouple inactivation from activation. 1994, Pubmed
Chen, A unique role for the S4 segment of domain 4 in the inactivation of sodium channels. 1996, Pubmed , Xenbase
Dib-Hajj, Sodium channels in normal and pathological pain. 2010, Pubmed
Dib-Hajj, NaN, a novel voltage-gated Na channel, is expressed preferentially in peripheral sensory neurons and down-regulated after axotomy. 1998, Pubmed
Goldin, Diversity of mammalian voltage-gated sodium channels. 1999, Pubmed
King, Peptide toxins that selectively target insect Na(V) and Ca(V) channels. 2008, Pubmed
Kontis, Sodium channel inactivation is altered by substitution of voltage sensor positive charges. 1997, Pubmed , Xenbase
Kontis, Sodium channel activation gating is affected by substitutions of voltage sensor positive charges in all four domains. 1997, Pubmed , Xenbase
Liman, Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs. 1992, Pubmed , Xenbase
Loughney, Molecular analysis of the para locus, a sodium channel gene in Drosophila. 1989, Pubmed
Maertens, Potent modulation of the voltage-gated sodium channel Nav1.7 by OD1, a toxin from the scorpion Odonthobuthus doriae. 2006, Pubmed , Xenbase
Moran, Sea anemone toxins affecting voltage-gated sodium channels--molecular and evolutionary features. 2009, Pubmed
Moran, Molecular analysis of the sea anemone toxin Av3 reveals selectivity to insects and demonstrates the heterogeneity of receptor site-3 on voltage-gated Na+ channels. 2007, Pubmed , Xenbase
Moran, Intron retention as a posttranscriptional regulatory mechanism of neurotoxin expression at early life stages of the starlet anemone Nematostella vectensis. 2008, Pubmed
Nicholson, Structure and function of delta-atracotoxins: lethal neurotoxins targeting the voltage-gated sodium channel. 2004, Pubmed
Oliveira, Binding specificity of sea anemone toxins to Nav 1.1-1.6 sodium channels: unexpected contributions from differences in the IV/S3-S4 outer loop. 2004, Pubmed
Rogers, Molecular determinants of high affinity binding of alpha-scorpion toxin and sea anemone toxin in the S3-S4 extracellular loop in domain IV of the Na+ channel alpha subunit. 1996, Pubmed
Roy, Differential properties of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in rat dorsal root ganglion neurons. 1992, Pubmed
Saab, Molecular determinant of Na(v)1.8 sodium channel resistance to the venom from the scorpion Leiurus quinquestriatus hebraeus. 2002, Pubmed
Salceda, The sea anemone toxins BgII and BgIII prolong the inactivation time course of the tetrodotoxin-sensitive sodium current in rat dorsal root ganglion neurons. 2002, Pubmed
Salceda, CgNa, a type I toxin from the giant Caribbean sea anemone Condylactis gigantea shows structural similarities to both type I and II toxins, as well as distinctive structural and functional properties(1). 2007, Pubmed
Salceda, Effects of ApC, a sea anemone toxin, on sodium currents of mammalian neurons. 2006, Pubmed
Sheets, The Na channel voltage sensor associated with inactivation is localized to the external charged residues of domain IV, S4. 1999, Pubmed
Song, RNA editing generates tissue-specific sodium channels with distinct gating properties. 2004, Pubmed , Xenbase
Ständker, A new toxin from the sea anemone Condylactis gigantea with effect on sodium channel inactivation. 2006, Pubmed
Stühmer, Structural parts involved in activation and inactivation of the sodium channel. 1989, Pubmed , Xenbase
Tan, Alternative splicing of an insect sodium channel gene generates pharmacologically distinct sodium channels. 2002, Pubmed , Xenbase
Thomsen, Localization of the receptor site for alpha-scorpion toxins by antibody mapping: implications for sodium channel topology. 1989, Pubmed
Ulbricht, Sodium channel inactivation: molecular determinants and modulation. 2005, Pubmed
Wanke, Actions of sea anemone type 1 neurotoxins on voltage-gated sodium channel isoforms. 2009, Pubmed
West, A cluster of hydrophobic amino acid residues required for fast Na(+)-channel inactivation. 1992, Pubmed , Xenbase
Yamaji, Synthesis, solution structure, and phylum selectivity of a spider delta-toxin that slows inactivation of specific voltage-gated sodium channel subtypes. 2009, Pubmed , Xenbase
Zaharenko, Revisiting cangitoxin, a sea anemone peptide: purification and characterization of cangitoxins II and III from the venom of Bunodosoma cangicum. 2008, Pubmed
Zaza, Pathophysiology and pharmacology of the cardiac "late sodium current.". 2008, Pubmed