Article Figures & Data
Figures
- Fig. 1.
Subunit structure of the voltage-gated sodium channels. The primary structures of the subunits of the voltage-gated sodium channels are illustrated as transmembrane folding diagrams. Cylinders represent probable α-helical segments. Bold lines represent the polypeptide chains of each subunit, with length approximately proportional to the number of amino acid residues in the brain sodium channel subtypes. The extracellular domains of the β1 and β2 subunits are shown as immunoglobulin-like folds. Ψ, sites of probable N-linked glycosylation; P, sites of demonstrated protein phosphorylation by protein kinase A (circles) and protein kinase C (diamonds); EEDD, outer, and DEKA, inner rings of amino acid residues that form the ion selectivity filter and the tetrodotoxin binding site; h, inactivation particle in the inactivation gate loop. Sites of binding of α- and β-scorpion toxins, and a site of interaction between α and β1 subunits are also shown.
- Fig. 2.
Amino acid sequence similarity and phylogenetic relationships of voltage-gated sodium channel subunits. a, comparison of amino acid identity for rat sodium channels NaV1.1 through NaV1.9. The comparison was performed with Megalign in the program DNAStar (utilizing the Clustal method) for the four domains and the cytoplasmic linker connecting domains III and IV. b, phylogenetic relationships by maximum parsimony analysis of rat sodium channel sequences NaV1.1 through NaV1.9 and Nax. To perform the analysis, the amino acid sequences for all of the isoforms were aligned using Clustal W. The amino acid sequences in the alignments were then replaced with the published nucleotide sequences, and the nucleotide sequence alignments were subjected to analysis using the program PAUP*. Divergent portions of the terminal regions and the cytoplasmic loops between domains I–II and II–III were excluded from the PAUP* analysis. The tree was rooted by including the invertebrate sodium channel sequences during the generation of the tree, although these sequences are not shown in the figure.
Tables
Receptor Site Toxin or Drug Domains Neurotoxin receptor site 1 Tetrodotoxin, saxitoxin, μ-conotoxin IS5—S6, IIS5—S6, IIIS5—S6, IVS5—S6 Neurotoxin receptor site 2 Veratridine, batrachotoxin, grayanotoxin IS6, IVS6 Neurotoxin receptor site 3 α-Scorpion toxins, sea anemone toxins IS5—IS6, IVS3—S4, IVS5—S6 Neurotoxin receptor site 4 β-Scorpion toxins IIS1—S2, IIS3—S4 Neurotoxin receptor site 5 Brevetoxins, ciguatoxins IS6, IVS5 Neurotoxin receptor site 6 δ-conotoxins Not established Local anesthetic receptor site Local anesthetic drugs, antiarrhythmic drugs, antiepileptic drugs IS6, IIIS6, IVS6
