Fig. 6.
The D1610R mutation significantly reduced the sensitivity of Nav 1.5 to ApB. (A) The D1610R mutation decreased the ability of ApB to slow fast-inactivation of Nav 1.5. Current traces before (black lines) and after (gray lines) application of 100 nM ApB were induced by a 20-ms depolarizing potential of –10 mV from a holding potential of –100 mV. (B) The ratio of I5ms to peak current in the presence of 100 nM ApB. I5ms was shown as the current not inactivated at 5 ms in (A). (C) ApB positively shifted the I–V curve of Igp fluxing through hNav 1.5 DIV voltage-sensor mutant. (D) Single mutation D1610R abolished ApB sensitivity of DIV inward Igp. In both (C) and (D), Igp were elicited by the protocol as described in the legend of Supplemental Fig. 3. The subtraction of linear leak currents has been performed. Cells were held at –100 mV and pretreated with 1 μM TTX. All currents are normalized to the maximal control current amplitude. ApB concentration is 100 nM. Note that WT* means the triple C373Y/R800D/S802E mutant Nav 1.5 channel.