Figure 4.

The S664 and S667 phosphorylation sites regulate the voltage dependence of current activation, whereas the S671 phosphorylation site regulates the peak INa density. Currents were recorded as described in the legend to Fig. 3. (A–D) The voltage dependence of current activation is shifted toward more depolarized potentials in cells expressing NaV1.5-S664A (A), NaV1.5-S664E (A), NaV1.5-S667A (B), or NaV1.5-S667E (B) than in cells expressing NaV1.5-WT, whereas no significant differences are observed with the NaV1.5-T670 (C) or NaV1.5-S671 (D) phosphomutants. (E–H) The mean ± SEM peak INa densities are plotted as a function of test potential. The peak INa density is reduced in cells expressing NaV1.5-S671E (H), compared with cells expressing NaV1.5-WT, whereas no significant differences are observed with the other phosphomutants. Current densities, time- and voltage-dependent properties, and statistical comparisons across groups are provided in Table 4. GNa, sodium conductance.

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