Cathecholamines increase heart rate and contraction force. This effect is mainly mediated by their interaction with the β-adrenergic receptor (β- AR) and its downstream ability to modulate Ca2+ cycling and fluxes of a number of ions through specific channels across the cell membrane. The complex nature and broad cellular influence of the β-AR signaling cascade suggest that an integrative modelling approach is appropriate to size the relative weight of each of the single mechanisms by which β-adrenergic inputs modulate whole-cell action potential (AP) and Ca2+ handling in cardiac myocytes. To this aim, the ventricular AP was simulated by using the Luo-Rudy model and the transmural heterogeneity of the AP (epicardial, midmyocardial and endocardial cells) was reproduced. The β-AR stimulation was modelled by incorporating its effects on L-type Ca2+ current, phospholamban, IKr, IKs and Na+-K+ pump. Simulation of β-AR stimulation showed significant changes in the AP and in Ca2+ handling, depending on the cell type and on the levels of ion fluxes alterations due to β-adrenergic inputs. Notably, the occurrence of early- and delayed-afterdepolarizations (EADs and DADs respectively) was reproduced. EADs and DADs are suggested as mechanisms responsible for the arrhythmogenic effect of the adrenergic stimulation.

Simulated effects of sympathetic stimulation on the action potential of ventricular cardiomyocytes

GRANDI, ELEONORA;VECCHIETTI, STEFANIA;SEVERI, STEFANO;GIORDANO, EMANUELE DOMENICO;CAVALCANTI, SILVIO
2005

Abstract

Cathecholamines increase heart rate and contraction force. This effect is mainly mediated by their interaction with the β-adrenergic receptor (β- AR) and its downstream ability to modulate Ca2+ cycling and fluxes of a number of ions through specific channels across the cell membrane. The complex nature and broad cellular influence of the β-AR signaling cascade suggest that an integrative modelling approach is appropriate to size the relative weight of each of the single mechanisms by which β-adrenergic inputs modulate whole-cell action potential (AP) and Ca2+ handling in cardiac myocytes. To this aim, the ventricular AP was simulated by using the Luo-Rudy model and the transmural heterogeneity of the AP (epicardial, midmyocardial and endocardial cells) was reproduced. The β-AR stimulation was modelled by incorporating its effects on L-type Ca2+ current, phospholamban, IKr, IKs and Na+-K+ pump. Simulation of β-AR stimulation showed significant changes in the AP and in Ca2+ handling, depending on the cell type and on the levels of ion fluxes alterations due to β-adrenergic inputs. Notably, the occurrence of early- and delayed-afterdepolarizations (EADs and DADs respectively) was reproduced. EADs and DADs are suggested as mechanisms responsible for the arrhythmogenic effect of the adrenergic stimulation.
2005
E. Grandi; S. Vecchietti; S. Severi; E. Giordano; S. Cavalcanti
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/30507
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