Table 3. Current densities and properties of NaV1.5 channels mutant for the phosphorylation clusters in transiently transfected HEK-293 cells.
| INa (pA/pF) | Time to peak (ms) | Time course of inactivation | Voltage-dependence of activation | Voltage-dependence of inactivation | Recovery from inactivation | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| τfast (ms) | τslow (ms) | Afast/Aslow | V1/2 (mV) | k (mV) | V1/2 (mV) | k (mV) | τrec (ms) | |||
| NaV1.5-WT | −130.8 ± 13.1 (25) | 0.60 ± 0.01 (19) | 0.72 ± 0.02 (18) | 3.6 ± 0.2 (18) | 15.5 ± 1.0 (18) | −45.7 ± 0.6 (19) | 6.8 ± 0.2 (19) | −88.3 ± 0.6 (19) | 4.9 ± 0.1 (19) | 8.7 ± 0.6 (19) |
| NaV1.5-S36-42A | −115.7 ± 11.2 (35) | 0.63 ± 0.02 (19) | 0.75 ± 0.02 (19) | 3.6 ± 0.2 (19) | 13.3 ± 1.0 (19) | −44.7 ± 0.6 (19) | 6.7 ± 0.1 (19) | −86.5 ± 0.8 (19) | 4.9 ± 0.1 (19) | 7.1 ± 0.6 (18) |
| NaV1.5-S36-42E | −92.2 ± 11.4 (31) | 0.59 ± 0.02 (19) | 0.72 ± 0.02 (17) | 3.5 ± 0.2 (17) | 13.6 ± 1.9 (17) | −45.2 ± 0.6 (19) | 6.6 ± 0.1 (19) | −86.1 ± 0.5 (19) | 4.6 ± 0.1 (19) | 7.3 ± 0.3 (18) |
| NaV1.5-S457-460A | −136.5 ± 12.1 (24) | 0.60 ± 0.01 (18) | 0.75 ± 0.02 (18) | 4.6 ± 0.4 (18) | 15.6 ± 1.2 (18) | −45.4 ± 0.7 (18) | 7.0 ± 0.2 (18) | −90.0 ± 0.9 (18) | 5.2 ± 0.1 (18) | 9.3 ± 0.5 (18) |
| NaV1.5-S457-460E | −123.3 ± 11.6 (28) | 0.60 ± 0.02 (20) | 0.74 ± 0.02 (19) | 3.7 ± 0.2 (19) | 17.5 ± 1.8 (19) | −45.2 ± 0.4 (20) | 6.8 ± 0.1 (20) | −87.5 ± 0.5 (19) | 4.7 ± 0.1 (19) | 8.7 ± 0.4 (19) |
| NaV1.5-S483-486A | −104.7 ± 11.3 (40) | 0.61 ± 0.02 (28) | 0.61 ± 0.02 (26) | 3.2 ± 0.1 (26) | 12.7 ± 1.0 (26) | −47.1 ± 0.6 (28) | 6.3 ± 0.2 (28) | −89.1 ± 0.7 (28) | 5.0 ± 0.1 (28) | 7.1 ± 0.5 (26) |
| NaV1.5-S483-486E | −117.4 ± 10.4 (29) | 0.55 ± 0.02 (19) | 0.59 ± 0.02 (16) | 2.9 ± 0.2 (16) | 14.2 ± 1.2 (16) | −48.2 ± 0.6 (19) | 6.3 ± 0.2 (19) | −89.6 ± 0.6 (19) | 4.8 ± 0.1 (19) | 8.2 ± 0.6 (16) |
| NaV1.5-S497-499A | −110.5 ± 13.5 (25) | 0.62 ± 0.02 (16) | 0.76 ± 0.03 (12) | 4.6 ± 0.4 (12) | 18.0 ± 1.4 (12) | −44.6 ± 0.6 (16) | 7.1 ± 0.1 (16) | −88.4 ± 0.7 (16) | 4.8 ± 0.1 (16) | 8.8 ± 0.7 (15) |
| NaV1.5-S497-499E | −129.5 ± 13.8 (22) | 0.56 ± 0.01 (18) | 0.70 ± 0.02 (17) | 3.8 ± 0.2 (17) | 16.7 ± 1.0 (17) | −46.7 ± 0.5 (18) | 7.2 ± 0.1 (18) | −90.2 ± 0.7 (18) | 4.9 ± 0.1 (18) | 9.5 ± 0.6 (18) |
| NaV1.5-S664-671A | −109.8 ± 11.8 (19) | 0.83 ± 0.02*** (18) | 0.89 ± 0.02** (17) | 5.5 ± 0.5* (17) | 18.1 ± 1.2 (17) | −35.1 ± 0.6*** (18) | 7.3 ± 0.1 (18) | −87.1 ± 0.6 (18) | 5.4 ± 0.1 (18) | 8.4 ± 0.4 (18) |
| NaV1.5-S664-671E | −74.5 ± 10.2# (23) | 0.80 ± 0.02*** (18) | 0.90 ± 0.03* (15) | 4.9 ± 0.4 (15) | 18.8 ± 1.9 (15) | −39.1 ± 0.4*** (18) | 7.0 ± 0.1 (18) | −86.1 ± 0.8 (18) | 5.1 ± 0.1 (18) | 7.7 ± 0.6 (16) |
| NaV1.5-S664-671D | −92.2 ± 13.2 (18) | 0.65 ± 0.02 (14) | 0.77 ± 0.03 (12) | 3.7 ± 0.2 (12) | 15.5 ± 1.7 (12) | −48.7 ± 0.6 (14) | 5.9 ± 0.2 (14) | |||
| NaV1.5-S1003-1010A | −103.0 ± 8.5 (38) | 0.62 ± 0.01 (19) | 0.76 ± 0.02 (19) | 4.2 ± 0.2 (19) | 7.4 ± 0.7 (19) | −45.3 ± 0.5 (19) | 6.5 ± 0.2 (19) | −86.6 ± 0.7 (19) | 6.0 ± 0.2 (19) | 6.7 ± 0.6 (19) |
| NaV1.5-S1003-1010E | −99.9 ± 11.9 (23) | 0.61 ± 0.01 (15) | 0.74 ± 0.02 (15) | 3.9 ± 0.1 (15) | 7.8 ± 0.6 (15) | −45.8 ± 0.8 (15) | 6.5 ± 0.2 (15) | −86.2 ± 0.8 (15) | 5.6 ± 0.2 (15) | 6.4 ± 0.5 (13) |
| NaV1.5-S1964-1969A | −115.0 ± 7.4 (23) | 0.63 ± 0.01 (21) | 0.77 ± 0.02 (20) | 4.1 ± 0.2 (20) | 15.8 ± 0.9 (20) | −44.9 ± 0.5 (21) | 6.6 ± 0.2 (21) | −87.6 ± 0.5 (21) | 5.1 ± 0.1 (21) | 7.8 ± 0.4 (18) |
| NaV1.5-S1964-1969E | −132.8 ± 18.3 (26) | 0.66 ± 0.02 (17) | 0.81 ± 0.02 (15) | 4.0 ± 0.2 (15) | 13.9 ± 0.8 (15) | −44.1 ± 0.6 (17) | 7.2 ± 0.2 (17) | −89.3 ± 0.8 (17) | 4.9 ± 0.1 (17) | 9.3 ± 0.8 (15) |
Whole-cell voltage-gated INa were recorded 48 h following transfection of HEK-293 cells with the WT or the mutant NaV1.5 channels and the NaVβ1 channel subunit using the protocols described in the Materials and methods section. The peak INa density, time to peak, and time course of inactivation properties presented were determined from analyses of records obtained on depolarizations to −20 mV (HP = −120 mV). All values are means ± SEMs. The number of cells analyzed is provided in parentheses. #, P < 0.05 versus NaV1.5-WT, one-way ANOVA followed by Dunnett’s post-hoc test. *, P < 0.05; **, P < 0.01; ***, P < 0.001 versus NaV1.5-WT; Kruskal-Wallis followed by Dunn’s post-hoc test.