Human Atrial Cell Models to Analyse the Effect of Extracellular Calcium on Action Potential Duration

Regulation of cardiac electrical and mechanical activities are highly dependent on L-type calcium current (ICaL). Moreover, the phenomenon of ICaL. inactivation plays a crucial role in adjusting action potential repolarization. This paper investigates the relationship between extracellular calcium concentration, [Ca+2]o, and action potential (AP). In particular, calcium-dependent inactivation (CDI) of ICaL has been analyzed to quantify its dependence on [Ca+2] o and its impact on AP duration. We have analyzed three human atrial cell models (hAM) by testing benchmarks like AP, ICaL, and INcx (sodium-calcium exchange current) with the variation of [Ca+2]o. The role of CDI was assessed by simulating the AP-clamp technique followed by 1) running the baseline model under normal CDI mechanism and 2) running the model without the CDI mechanism. The comparison of three hAMs shows that besides the contribution of CDI, driving force (DF), and INCX current should also be considered while studying the relationship between AP duration (APD) and [Ca+2] o. None of the hAMs reproduced in a physiologically correct way the effects of [Ca+2]o on APD, therefore our results call for a new hAM able to reproduce correctly the [Ca+2]o effect