Structurally, sodium channels are comprised of four domains (DI–DIV), each composed of six transmembrane segments (S1–S6), with S4 carrying a positively-charged residue at every third amino
Sorafenib Tosylate and segments S1–S4 act as the voltage sensor [14]. Depolarizing voltage steps lead to an outward movement of these gating charges, followed by a conformational change inducing the transient opening of the channel pore and sodium ion flow within less than a millisecond. Mutations of S4 segments have been linked to inherited skeletal, cardiac and CNS sodium channelopathies [15], [16] and [17], including IEM [18]. In this study, we used whole-cell patch-clamp recordings to investigate the effects on channel gating of the IEM
mutation L823R [19], which introduces an additional positive charge into the DII/S4 (Fig. 1). The introduction of a sixth positively-charged residue to DII/S4 is predicted to make the channel more sensitive to voltage changes, so that the S4 should respond to a weaker depolarizing stimulus, compared to wild-type channels.
