A,B: time-courses of current amplitudes (left panels) and sample current traces (right panels: a, control; b, steady-state block) recorded at −140 mV before, during, and after superfusion with 30 µM ivabradine (horizontal bars). Horizontal bars in right panels: 150 ms. C: Dose-response relations of ivabradine block of WT and mutant channels. Fitting with the Hill equation (curves) yielded half-block concentrations (IC50) of 2.1, 3.1, 3.6, 57.7, 3.7, 1.9, 44.0, 47.7 µM and Hill coefficients (nH) of 0.74, 0.84, 0.72, 1.02, 0.75, 0.77, 0.73, 0.83 for WT, C478A, A503V, Y506A, A507V, M508A, F509A, and I510A channels, respectively. Dose-response relations for Y506A, F509A, and I510A curves are significantly different from WT (P<0.05).