Figure 4
Rate-dependent effects of potassium channel blockers. (A–D) Representative averaged FP (left) and FPD values (right) in control conditions (black) and after drug application (red). (A) Effects of 100 µM Sotalol on FPD at 1 Hz (+30.4 ± 3.5%, n = 6 from 4 batches, p = 0.0003), 1.5 Hz (+9.1 ± 2.4%; n = 10 from 4 batches; p = 0.006) and 2 Hz (+0.1 ± 2.3%, n = 7 from 3 batches, p = 0.76), (B) Effect of 50 nM E4031 at 1 Hz (+24.6 ± 3.7%, n = 4 from 3 batches, p = 0.013), 1.5 Hz (+7.5 ± 4.0%, n = 7 from 3 batches, p = 0.1) and 2 Hz (−2.8 ± 3.1%, n = 4 from 3 batches, p = 0.4542). (C) Effect of 25 nM (red) JNJ303 in FPD at 1 Hz (+10.9 ± 2.5%, n = 3 from 2 batches, p = 0.105), 1.5 Hz (−3.3 ± 4.2%, n = 3 from 2 batches, p = 0.614), 2 Hz (−2.4 ± 2.4%, n = 3 from 2 batches, p = 0.508) and of 100 nM (green) JNJ303 at 1 Hz (+6.7 ± 5.2%, n = 3 from 2 batches, p = 0.381), 1.5 Hz (−10.2 ± 8.4%, n = 3 from 2 batches, p = 0.442) and 2 Hz (−11.3 ± 7.3%, n = 3 from 2 batches, p = 0.341). (D) Effect of low-dose 10 µM Sotalol at 1.5 Hz on FPD (red, + 10.6 ± 7.0, n = 7 from 1 batch, p = 0.17) and additional 100 nM JNJ303 (green, compared to control: + 22.1 ± 3.3%, p < 0.0001; compared to Sotalol: + 11.8 ± 4.3%, p = 0.03; n = 7 from 1 batch). Note that stable pacing >1.5 Hz was not possible (n = 7) after applying JNJ303 and Sotalol. Significances were determined using two-tailed, paired student’s t-tests. *p < 0.05, **p < 0.01, ***p < 0.001.
