Fig. 1

Localization of the E452K variant in hNaV1.4. (A) Sanger sequencing of a portion of exon 9 revealed the heterozygous mutation c.1354G > A that causes the E452K substitution. (B) The E452K mutation is in a region that is highly conserved in all voltage-gated sodium channels in humans and other species. (C) Schematic representation of the hNaV1.4 α-subunit highlighting the localization of the E452K mutation on the intracellular loop between domain I and domain II. (D) Side view of the α-subunit illustrating its four domains (I to IV) along with its β1 regulatory subunit. (E) Intracellular view of the channel protein illustrating the open pore cavity in the center, the four domains (I to IV), and the inactivation gate (III-IV linker). (F) A higher resolution view of the I-II linker, pinpointing the position of the glutamate (E) residue.