Figure 9. Effects of ibrutinib and acalabrutinib on the rapid delayed rectifier K⁺ current (IKr) in isolated sinoatrial node (SAN) myocytes.

A, Representative I_Kr recordings in isolated SAN myocytes at baseline and after application of 10 µmol/L of ibrutinib of (IBR (10)). Voltage clamp protocol shown below recordings. B, Peak total K⁺ current (I_K(tot)) I‐V curves, measured at the end of the 1‐second depolarizing steps, at baseline and after application of IBR (10). C, Boltzmann fit of I_Kr tail currents (measured at −45 mV) at baseline and after application of IBR (10). D, Voltage for 50% channel activation (V_1/2(act)) for I_Kr tail current at baseline and after application of IBR (10). For panels B–C: *P<0.05 vs baseline by 2‐way repeated measures ANOVA with a Tukey post hoc test; for panel D: *P<0.05 vs baseline by paired Student t test; n=7 SAN myocytes from 3 mice. E, Representative I_Kr recordings in isolated SAN myocytes at baseline and after application of 10 µmol/L of acalabrutinib (ACAL (10)). F, Peak I_K I‐V curves, measured at the end of the 1‐second depolarizing steps, at baseline and after application of ACAL (10). G, Boltzmann fit of I_Kr tail currents (measured at −45 mV) at baseline and after application of ACAL (10). D, V_1/2(act) for I_Kr tail current at baseline and after application of ACAL (10). For panels F–G: data analyzed by 2‐way repeated measures ANOVA with a Tukey post hoc test; for panel H: data analyzed by paired Student t test; n=5 SAN myocytes from 3 mice.