Figure 11. Open-channel block of hNav1.5-L409C/A410W and hNav1.5-L409C/A410W/1760K at various mexiletine concentrations.

Superimposed current traces of hNav1.5-L409C/A410W (A) or hNav1.5-L409C/A410W/F1760K (B) mutant channels were recorded with a test pulse at +30 mV for 50 ms before and after mexiletine at various concentrations. Notice that mutation F1760K renders the open channel relatively resistant to mexiletine block. C, dose–response curves for open-channel block (relative block at end of 50 ms test pulse to +30 mV) and resting-state block (relative block of peak currents) were constructed using the data set as shown in A and B. Data were fitted with the Hill equation. IC₅₀ values ±s.e.m. [Hill coefficients ±s.e.m.] for hNav1.5-L409C/A410W are 11.1 ± 0.3 μm[1.1 ± 0.2] for open-channel block (▪, n= 5), and 157.4 ± 11.4 μm[1.2 ± 0.1] for resting-state block (□, n= 6). IC₅₀ values ±s.e.m. [Hill coefficients ±s.e.m.] for hNav1.5-L409C/A410W/F1760K are 207.9 ± 7.0 μm[1.0 ± 0.1] for open-state block (•, n= 5), and 290.7 ± 9.6 μm[1.1 ± 0.1] for resting-state block (○, n= 5).