Previous studies showed that the timing of peak Na-Ca exchanger current (INCX) activity is coincidental with the maximum slope of intracellular calcium (Cai) decline (-(dCai/dt)max). We performed simultaneous membrane potential (Vm) and Cai mapping in 14 isolated rabbit ventricles to test the hypothesis that the timing of -(dCai/dt)max is coincidental with the anodal dip on the strength-interval (SI) curve and the onset of first non-driven beats of the repetitive responses or VF induced by a premature stimulus (S2). A dip was reproducibly observed in the anodal SI curve. During the anodal dip, ventricles were captured by anodal break excitation directly under the S2 electrode. The timing of anodal dip (203 짹 10 ms after last pacing stimulus) was essentially the same as the timing of the -(dCai/dt)max (200 짹 11 ms, P=NS). BAPTA-AM and ZD 7288 both eliminated the anodal dip. Strong S2 induced 24 repetitive response and 10 ventricular fibrillations (VF) episodes. The S2 induced graded responses and Cai elevation in most tissues near the S2, but a small region showed continued and rapid Cai decline. This region formed a ���Cai sinkhole���, defined by a lower Cai than surrounding sites. The first non-driven beats of the repetitive response (blue arrow in Fig B) and VF originated from that Cai sinkhole, at 129 짹 30 ms after S2, coincidental with the -(dCai/dt)max (black arrow) at 129 짹 32 ms (p=NS). We conclude that INCX reduced the excitation threshold during anodal dip, and played an important role in the mechanisms of ventricular vulnerability.