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. 2009 Mar 27;284(13):8846–8854. doi: 10.1074/jbc.M806871200

FIGURE 2.

FIGURE 2.

CaM-binding domains in the C terminus and DIII--DIV linker region control the effects of lidocaine on NaV1.5 steady-state availability. A, voltage dependence of inactivation in cells expressing WT, A1924T, or FIF/AAA (1.5 μg cDNA each) in low or high [Ca2+]i. In high [Ca2+]i, WT, A1924T, and FIF/AAA V½ of inactivation were not significantly different (-71.3 ± 0.9 mV (•; n = 24), -74.7 ± 1.9 mV (▴; n = 13), and -73.7 ± 1.0 mV (▪; n = 13), respectively (p = NS)). In low [Ca2+]i, the V½ of inactivation of WT significantly differed from A1924T and FIF/AAA (-79.6 ± 1.0 mV (○; n = 22), -87.4 ± 1.2 mV (▵; n = 11; p < 0.05), and -85.9 ± 0.9 mV (□; n = 9; p < 0.05), respectively). B, V½ for A1924T in the absence or presence of lidocaine in high [Ca2+]i was -74.7 ± 1.9 mV (•; n = 13) and -75.4 ± 1.4 mV (○; n = 9), respectively (p = NS). Left inset, voltage-dependent inactivation for WT NaV1.5 under the same conditions. Right inset, representative current traces in 1 μm [Ca2+]i, in the presence (left) or absence (right) of lidocaine. Black traces show currents obtained at -20 mV after a prepulse at -160 mV, the small lines show the currents obtained after a prepulse at -80 mV. Decay rates of the currents at -20 mV after a prepulse to -160 mV were fit with the sum of two exponential components. The biexponential decay rates of A1924T in high [Ca2+]i in the absence (τf = 0.51 ± 0.02; τs = 2.46 ± 0.17) and presence of lidocaine (τf = 0.57 ± 0.05; τs = 2.42 ± 0.26) were not different (p = NS). C, voltage-dependent inactivation of NaV1.5 FIF/AAA in the absence or presence of lidocaine in high [Ca2+]i. V½ was -73.7 ± 1.0 mV (•; n = 13) in the absence and -74.1 ± 0.6 mV (○; n = 5) in the presence of lidocaine (p = NS). Left inset, same as in B. Right inset, representative NaV1.5 FIF/AAA currents in 1 μm Cai, in the presence (left) or absence (right) of lidocaine. Color coding is as described in B. The biexponential decay rates of NaV1.5 FIF/AAA in high [Ca2+]i in the absence (τf = 0.54 ± 0.03; τs = 2.7 ± 0.33), and presence of lidocaine (τf = 0.52 ± 0.05; τs = 2.27 ± 0.42) were not different (p = NS). D, shifts in the V½ of steady-state inactivation of NaV1.5 WT, A1924T, and FIF/AAA with or without 50, 300, or 2000 μm lidocaine in high [Ca2+]i from B and C and Fig. 1A.