Variable splicing of Na_v1.1. (A) Predicted membrane topology of Na_v1.1 with the 4x6 organization typical for voltage-gated sodium channels, namely four homologous domains (D1–D4) comprising six transmembrane regions each (S1–S6, from left to right). Amino- and carboxytermini end on the intracellular side. Arrows denote where differential splicing creates sequence variability in the final protein. Solid arrow: point where splice variants lack either 11 or 28 amino acids compared to full-length Na_v1.1. Open arrows: amino acid differences owing to alternate encoding via exon 5N or 5A [41] as outlined in Table 1. (B) Alignment of the full-length Nav1.1 protein sequence with that of Na_v1.1[-33] and Na_v1.1[-84] at the exon 11/12 splice junction. Alternative endings of exon 11 create two shorter variants which omit residues 671–681 or 654–681. The isoform nomenclature refers to the nucleic acid level: compared to full-length Nav1.1 cDNA, the shorter isoforms miss 33 or 84 base pairs. Biochemical and electrophysiological analysis suggest a functional importance of the spliced fragments (personal observation).

_{Differences in amino acid coding between mutually exclusive exons 5N and 5A}

_{Topology abbreviations as described here.}