Figure 4. Loss of miR-19b induces prolongation of the action potential.

(a) Schematic illustration of an action potential with major depolarizing and repolarizing currents depicted. Terfenadine inhibits I_Kr current, thereby prolonging the ventricular action potential. (b) Atrial and ventricular m-mode recorded from control and MO19b-injected Tg(Myl7:GFP) zebrafish embryos after 30 μM Terfenadine treatment. (b,c) 25% ± 4.1% of miR-19b deficient embryos develop an AV-Block with the ventricle skipping every other contraction, whereas control injected embryos show no phenotype. (±sd; n = 3 with ≥10 animals per group; p < 0.05) (d,e) Patch-clamp Experiments revealed that morpholino-mediated loss of miR-19b results in prolonged action potentials with up to 57% ± 3.8% and 39% ± 3.5% prolongation of APD₅₀ and APD₉₀, respectively (±sd; n ≥ 10 from 5 hearts; p < 0.05). Additionally, the notch appeared to be less pronounced (stars).