A common cardiac sodium channel variant associated with sudden infant death in African Americans, SCN5A S1103Y
J. Clin. Invest. Leigh D. Plant, et al. 116:430 doi:10.1172/JCI25618 [Go to this article.]

Figure 5
Abnormal reopenings are suppressed by mexiletine. Single channels were studied in inside-out, off-cell patches as in Figure 3. (A) Dose-response curves for phasic block by mexiletine of peak macroscopic currents with S1103 (open squares) and Y1103 (filled squares) channels studied in whole-cell mode. Each point shows the average percent reduction in peak current by the dose indicated after a series of repetitive depolarizing stimuli (n = 3–7 cells). Cells were depolarized to –30 mV from a holding potential of –100 mV for 10 ms at 2.5 Hz to mimic a rate of 150 bpm. Inset: Representative S1103 current traces evoked by a pulse in drug-free solution (control) and the first (pulse 1) to show tonic block and fiftieth (pulse 50) to show phasic block by 10 μM mexiletine (mex). Values for tonic and phasic block by mexiletine, propranolol, and amiodarone are reported in Supplemental Table 4. (B) Single Y1103 channels studied in inside-out off-cell patches showed that late reopenings of variant channels were fully suppressed by 5 μM mexiletine. Null traces in the absence of drug (see Figure 3B) at pH 7.4 and 6.7 were 51% ± 4.5% (n = 8 patches, 742 sweeps) and 52 ± 2.5% (n = 10 patches, 942 sweeps), respectively; null traces at pH 6.7 with drug were 55% ± 3.5% (n = 6 patches, 561 sweeps). The therapeutic blood level of mexiletine is 0.8–2.0 μg/ml (3.7–9.3 μM). Scale bars: 2 ms, 200 pA (A); 0.3 pA, 10 ms (B).