ProTx‐II interacts with VSDI, II and IV (see superscript summary after ‘ProTx‐II’) in NaV1.2 to inhibit channel opening (see 2:2222 column). Top shows a current trace whereas bottom depicts a G–V relationship before (black) and after (red) application of 100 nm ProTx‐II. A small inhibitory effect was observed on WT NaV1.8 (8:8888 column). In contrast, 100 nm ProTx‐II strongly inhibits opening of the 8:2888 chimera. Current traces shown were recorded at voltages near the foot of the G–V curve for each construct (holding potential was −90 mV with 5 s between depolarizing pulses). V
1/2 = −27 ± 1 mV (2:2222 black), −8 ± 1 mV (2:2222 red), 4 ± 1 mV (8:8888 black), 6 ± 1 mV (8:8888 red), −6 ± 1 mV (8:2888 black), 9 ± 1 mV (8:2888 red). Error bars represent SEM, with n = 3.