We next tested whether enhanced RISK/SAFE pathway induction was causally linked to the reduced IR susceptibility in female versus male Kcne4−/− mice, by quantifying the effects on post-IR arrhythmia incidence of pharmacological inhibitors of ERK1/2 (U0126), AKT (wortmannin) and STAT3 (Ag490). Here, KCNE4 is linked to cardiac arrhythmia.