Calcium Transients Modulate Action Potential Repolarizations in Ventricular Fibrillation

Action potential alternans has been an indicator of ischemic disease and vulnerability to ventricular fibrillation (VF). The mechanisms of alternans are linked to the anomalies in intracellular Ca ²⁺ (Ca_i) handling by either spontaneous Ca²⁺ release or modulation of action potential duration (APD), which may promote wave breaks in VF. We investigated possible role of Ca²⁺ in wave breaks by simultaneously measuring transmembrane potential (V_m) and intracellular Ca²⁺ concentration with voltage sensitive dye (RH237) and Ca²⁺ (Rhod-2) fluorescence probes. VF was induced by burst stimulation and the relationship between V_m and Ca²⁺ oscillations in VF were analyzed with cross-correlation analysis. The maximum correlation occurred at 12 ms delay between V_m and Ca_i , suggesting V_m still triggers Ca²⁺ release in VF as in normal excitation-contraction coupling. In addition, inverse correlation was found -20 ms between V_m and Ca_i, suggesting the amplitude of Ca_i can modulate action potential recovery in VF. In conclusion, Ca_i can influence action potential durations, which may promote wave breaks in VF