FIGURE 4.

I_CaL and I_to characterization of Ctrl- and BrS-CMs. (A) Examples of original I_to traces elicited by 10 mV-step depolarization from −40 to 60 mV at a holding potential of −90 mV. Top, I_to in one Ctrl1-CM. Bottom, I_to in one BrS1-CM. (B) Average I–V relationships of the I_to current in Ctrl- and BrS-CMs. Protocol is shown as inset. (C) Average of the steady-state voltage dependence of inactivation I_to current in Ctrl- and BrS-CMs. The pulse protocol is shown as inset. No significant differences were observed. The I_to current density in Ctrl-CMs (D) and BrS-CMs (E) with and without 4-AP (1 mM) treatment for 1 min. (F) Average of recovery from inactivation of I_to current in Ctrl- and BrS-CMs. The pulse protocol is shown as inset. No significant differences were observed. Expression profile of I_to-related genes: KCND3 (G), KCND2 (H), KCNA4 (I), and TNNT2 (J). Data were presented relative to RPL32 expression (Ctrl: n = 6, BrS1: n = 6, BrS2: n = 6 independent differentiation experiments). (K) Examples of original I_CaL traces of a Ctrl2-CM and a BrS1-CM. (L) Average I–V relationships of the I_CaL in Ctrl-, BrS1-, and BrS2-CMs. The protocol is shown as inset. (M) The steady-state of activation (G/G_max) and steady-state of inactivation (I/I_max) are overlaid to show the window current of I_CaL. Window currents are the areas under the intersecting current–voltage curves. The impulse for inactivation is shown as inset. (N) The probability being within I_CaL window current is plotted. (O) Average of recovery from inactivation of I_CaL in Ctrl-, BrS1-, and BrS2-CMs. The pulse protocol is shown as inset. Data are presented as mean ± SEM. Two-way repeated measures ANOVA was used for I_to and I_CaL statistical analysis. One-way ANOVA was used for gene expression analyses. ^∗P < 0.05, #P < 0.01, §P < 0.001.