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
.