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.
Titolo: | Simulated effects of sympathetic stimulation on the action potential of ventricular cardiomyocytes |
Autore/i: | GRANDI, ELEONORA; VECCHIETTI, STEFANIA; SEVERI, STEFANO; GIORDANO, EMANUELE DOMENICO; CAVALCANTI, SILVIO |
Autore/i Unibo: | |
Anno: | 2005 |
Rivista: | |
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. |
Data prodotto definitivo in UGOV: | 28-set-2006 |
Appare nelle tipologie: | 4.01 Contributo in Atti di convegno |