Fig. 4.
The double mutation (D800R/E802S) abolished the ability of HWTX-IV to alter the inward Igp fluxing through DII voltage-sensor mutant. (A) Effects of HWTX-IV on the central-pore currents from the WT* and double mutant R800D/S802E Nav 1.5 channels. Current traces before (black) and after (gray) 1 μM HWTX-IV treatment were induced by a 20-ms depolarizing potential of –10 mV from a holding potential of –100 mV. (B) Fraction of remaining currents in the presence of 1 μM HWTX-IV. (C) HWTX-IV positively shifted the I–V curve of the inward Igp generated by hNav 1.5 DII voltage-sensor mutant (R1G/R2G). (D) Double mutation D800R/E802S abolished the effect of HWTX-IV on the inward Igp generated by DII voltage-sensor mutant (R1G/R2G). In both (C) and (D) Igp were elicited by the protocol as described in the legend of Supplemental Fig. 3. Cells were held at –100 mV and pretreated with 1 μM TTX. All currents are normalized to the maximal control current amplitude. Linear leak currents were subtracted.