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Fig. 5
HCN inhibitors reduce heart rate in developing zebrafish embryos. (A) Experimental method. Inhibitors were administered in the egg water at 24 hpf, and this time point was designated as ?0 h?. After administering the inhibitors, heart rate was measured at 24 h (24 h) and 48 h (48 h). Zebrafish were then transferred back to the inhibitor-free egg water, and their heart rates were measured 6 h later (washout). (B) Changes in heart rate with time in zebrafish before (control; grey; n = 10) and after treatment with 1 mM cesium ion (pink; n = 10), ZD7288 (orange; n = 10) and ivabradine (green; n = 10) inhibitors. Heart rates before (0 h) and at 24 h (24 h) and 48 h (48 h), after application of the inhibitors and at 6 h after washing out the inhibitors (washout) are shown as bar graphs. Dunnett?s test was used for statistical analysis, and Student?s t-test was used to compare before and after ?washout.? (C) Changes in heart rate with time in zebrafish treated with ZD7288 before (gray; n = 10) and after treatment with 10 ?M (light orange; n = 10), 100 ?M (orange; n = 10), and 1 mM (dark orange; n = 10). Dunnett?s test was used for statistical analysis, and Student?s t-test was used to compare before and after washout. (D) Changes in heart rate with time in zebrafish treated with ivabradine before (gray; n = 10) and after treatment with 10 ?M (thin green; n = 10), 100 ?M (light green; n = 10) and 1 mM (dark green; n = 10). Dunnett?s test was used for statistical analysis, and Student?s t-test was used to compare before and after washout.