Biophysical properties of INa in parents’ (WT, 1473F/F) and proband’s (LQT-3, 1473F/C) iPSC-CMs
| Na+ channel biophysical properties | WT | LQT-3 |
| INaL (%) | 0.02 ± 0.01 (n = 17, HR-I-2R 2Cr)0.01 ± 0.01 (n = 6, HR-I-7)0.04 ± 0.03 (n = 4, HR-I-15)0.04 ± 0.03 (n = 4, HR-II-5)0.002 ± 0.002 (n = 4, HR-II-9) | 0.71 ± 0.08 (n = 41, OA6 9Cr8)a0.55 ± 0.06 (n = 7, OA6 17Cr8)a0.91 ± 0.22 (n = 13, OA6 22Cr8)a |
| Steady-state inactivation (V1/2) (mV) | −68.5 ± 1.7 (n = 13, HR-I-2R 2Cr)−68.9 ± 0.9 (n = 6, HR-I-7)−69.5 ± 2.1 (n = 4, HR-I-15)−70.3 ± 1.7 (n = 3, HR-II-9) | −58.4 ± 0.8 (n = 21, OA6 9Cr8)a−59.8 ± 1.4 (n = 6, OA6 17Cr8)a |
| Recovery from inactivation(t1/2) (ms) | 60.4 ± 14.7 (n = 4, HR-I-2R 2Cr) | 6.14 ± 1.2 (n = 6, OA6 9Cr8)a |
| Activation (V1/2) (mV) | −25.5 ± 0.3 (n = 3, HR-II-9) | −26.1 ± 0.5 (n = 3, OA6 9Cr8) |
| Na+ channel biophysical properties | WT | LQT-3 |
| INaL (%) | 0.02 ± 0.01 (n = 17, HR-I-2R 2Cr)0.01 ± 0.01 (n = 6, HR-I-7)0.04 ± 0.03 (n = 4, HR-I-15)0.04 ± 0.03 (n = 4, HR-II-5)0.002 ± 0.002 (n = 4, HR-II-9) | 0.71 ± 0.08 (n = 41, OA6 9Cr8)a0.55 ± 0.06 (n = 7, OA6 17Cr8)a0.91 ± 0.22 (n = 13, OA6 22Cr8)a |
| Steady-state inactivation (V1/2) (mV) | −68.5 ± 1.7 (n = 13, HR-I-2R 2Cr)−68.9 ± 0.9 (n = 6, HR-I-7)−69.5 ± 2.1 (n = 4, HR-I-15)−70.3 ± 1.7 (n = 3, HR-II-9) | −58.4 ± 0.8 (n = 21, OA6 9Cr8)a−59.8 ± 1.4 (n = 6, OA6 17Cr8)a |
| Recovery from inactivation(t1/2) (ms) | 60.4 ± 14.7 (n = 4, HR-I-2R 2Cr) | 6.14 ± 1.2 (n = 6, OA6 9Cr8)a |
| Activation (V1/2) (mV) | −25.5 ± 0.3 (n = 3, HR-II-9) | −26.1 ± 0.5 (n = 3, OA6 9Cr8) |
INa late current (INaL) is expressed as a percentage of INa peak current. V1/2 (in millivolts) indicates the midpoint of steady-state inactivation and activation as determined by fitting data with the Boltzmann equation. t1/2 (in milliseconds) is the time for half of the channels to recover from inactivation. Values are reported as means ± SEM. Indicated in parentheses are the number of cells tested (n) and clone names (father, HR-I-2R 2Cr, HR-I-7, and HR-I-15; mother, HR-II-5 and HR-II-9; proband, OA6 9Cr8, OA6 17Cr8, and OA6 22Cr8). Statistical significance was determined with an unpaired Student’s t test. With the exception of activation midpoint, all data measured in LQT-3 iPSC-CMs were significantly different from the corresponding data obtained in WT cells. Data obtained from different clones within each group (WT or LQT-3) are not significantly different from each other.
P < 0.05.