Ionic basis of arrhythmic risk biomarkers on simulated rabbit ventricular myocytes

Cardiac proarrhythmic risk can be estimated considering several biomarkers based on electrophysiological properties. The aim of this work is to identify the key ionic mechanisms predicting arrhythmia generation in rabbit hearts at the cellular level. For this purpose, the sensitivity of action potential (AP) duration (APD), AP triangulation, AP rate dependence and intracellular calcium and sodium levels to variations in transmembrane ionic current conductances was analyzed. Simulations show that, in rabbit, APD is moderately influenced by changes in all repolarization current conductances, highlighting I_NaK, I_CaL and I_Kr. AP triangulation, however, is basically determined by I_Kl and I_Kr. In addition, AP rate dependence is especially sensitive to I_NaK, I_NaCa, I_Kr and I_CaL. Furthermore, intracellular calcium and sodium levels are highly determined by I_CaL, I_NaK and I_NaCa.