Figure 7.

ICA-105574 reverses the effects of E-4031. (A) After impalement and Vm stabilization, bath application of E-4031 leads to progressive widening of the AP plateau such that at time point (c) there are multiple secondary “spikes”. The subsequent addition of 1 μM ICA-105574 in the continued presence of E-4031 leads to the narrowing of some (arrowheads) but not all APs, whereas 3 mM ICA-105574 consistently reduces plateau duration (e) to values lower than control (a). (B) Expanded time scales show how the duration of the plateau phase of the AP is altered first by the addition of E-4031 and then subsequent addition of ICA-105574. Individual APs marked (a–e) correspond to the times marked (a–e) in (A). Calibration bar: 10 mV·2 s⁻¹ for all traces except (c) where it is 10 mV·5.8 s⁻¹. (C,D) Summary data for 4 vessels from 2 animals, using either the raw (C) or normalized (D, to control) data for AP plateau duration. The concentration of E-4031 was 100 nM; the concentration of ICA-105574 was 3 μM. Error bars are ± SD. Significance determined using a one-way ANOVA with Tukey’s multiple comparison tests. *Indicates p < 0.05; **indicates p < 0.01; ***indicates p < 0.001; ns = not significant at p < 0.05.