Inhibition of atrial action potentials alternans by calcium-activated chloride current blockade - simulation study

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Atrial action potential (AP) alternans appearance during atrial flutter play a determinant role as AF precursor. AP alternans involves intracellular calcium concentration alternation that affects calcium dependent currents like I_NaCa und I_ClCa. In this study, a modified rabbit atrial AP mode, that includes I_ClCa formulation is used. In order to induce alternans, the pacing cycle length was abruptly shortened from a basic drive of 1000 ms after 7.5 s of stimulation. The role of I_ClCawas investigated by blocking the current. When increasing pace rate, from a cycle length of 1000 ms to 180 ms, beat-to-beat alternans appear. Repeating the procedure in I_ClCablockade situation, in the range of 60 to 100 %, alternans disappear. Our results suggest that I_ClCa blockade prevents alternans and for this reason I_ClCa blockade could be potentially antiarrhythmic, preventing AF.