Dependence of action potential duration on extracellular calcium concentration in a model of human ventricular myocyte

The mechanisms underlying the inverse relation between extracellular calcium concentration ([Ca
²⁺
]
_O
) and action potential duration (APD) in ventricular myocytes are not fully clear. We computationally analysed the effects of [Ca
²⁺
]
_O
variations on APD of human cardiac myocyte by means of the Ten Tusscher (2004) model. The I
_CaL
current description was then modified in order to make the simulated results coherent with experimental findings. The original model formulation produced opposite results with respect to the expected trend, i.e. an increase of APD when ([Ca
²⁺
]
_O
was observed. By strengthening the Ca
²⁺
-dependent inactivation of I
_CaL
it was possible to reproduce the reduction of APD when increasing [Ca
²⁺
]
_O
. The mechanism of Ca -dependent I
_CaL
inactivation seems to be an high sensible pathway for APD adaptation to variations in ([Ca
²⁺
]
_O
.