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 4
Single Y1103 channels show abnormal late reopenings. Single channels studied in inside-out, off-cell patches excised from HEK-293 cells. Currents were stimulated every 2.5 seconds by a 50-ms depolarizing pulse to –30 mV from a holding potential of –120 mV. Data were recorded at filter and sampling frequencies of 5 and 50 kHz, respectively. Pipettes were filled with bath solution described in Methods. Cells were perfused with the pipette solution described in Methods. For each cell, null sweeps (with no channel activity) were identified, averaged offline, and subtracted from data sweeps before analysis. For display purposes, data were refiltered offline using a 2-kHz Bessel filter. (A) With depolarization, single S1103 channels opened, inactivated rapidly, and did not reopen. This behavior was unaltered when internal pH was lowered from 7.4 to 6.7. Null traces at pH 7.4 and 6.7 were 50% ± 2.7% (n = 15 patches, 1,367 sweeps) and 51% ± 3.4% (n = 12 patches, 1,028 sweeps), respectively. In contrast, Y1103 channels behaved like S1103 channels at pH 7.4 but showed late reopenings at pH 6.7. Null traces were 51% ± 4.5% at pH 7.4 (n = 8 patches, 742 sweeps) and 51.7 ± 2.5% (n = 10 patches, 942 sweeps) when pH was reduced to 6.7. (B) Ensemble average traces (n = 100–150 sweeps) for the indicated channels and conditions. Y1103 channels failed to remain in the inactivated state when exposed to internal pH 6.7. Scale bars: 0.5 pA; 10 ms.