Effects Of β-adrenergic Stimulation On The
Ventricular Action Potential: A Simulation Study
Author(s)
E. Grandi, S. Vecchietti, S. Severi, E. Giordano & S. Cavalcanti
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 suggests 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. The ventricular AP
was simulated by using the Luo-Rudy model. The transmural heterogeneity of
the AP (epicardial, mid-myocardial and endocardial cells) was reproduced by
considering three different levels of expression of the transient outward current
(ITo) and three different ratios of the slow vs. the rapid component of the delayed
rectifier K+ current (IKs / IKr). The β-AR stimulation was modelled by
incorporating its effects on L-type Ca2+ current, phospholamban, IKr, IKs, Na+-K+
pump and Na+/Ca2+ exchanger. 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-after-depolarizations (EADs and DADs
respectively) was also reproduced. In the present analysis, EADs and DADs are
suggested as mechanisms responsible for the arrhythmogenic effect of the
adrenergic stimulation.
Keywords: β-adrenergic stimulation, computer modelling, arrhythmia.
Keywords
β-adrenergic stimulation, computer modelling, arrhythmia.
Related Book
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