Iancu2007_CardiacMyoscytes_cAMPsignaling

This a model from the article:
Compartmentation of cAMP signaling in cardiac myocytes: a computational study.

Iancu RV, Jones SW, Harvey RD. Biophys J
2007 May 1;92(9):3317-31 17293406
,
Abstract:

Receptor-mediated changes in cAMP production play an essential role in
sympathetic and parasympathetic regulation of the electrical, mechanical, and
metabolic activity of cardiac myocytes. However, responses to receptor
activation cannot be easily ascribed to a uniform increase or decrease in cAMP
activity throughout the entire cell. In this study, we used a computational
approach to test the hypothesis that in cardiac ventricular myocytes the effects
of beta(1)-adrenergic receptor (beta(1)AR) and M(2) muscarinic receptor (M(2)R)
activation involve compartmentation of cAMP. A model consisting of two
submembrane (caveolar and extracaveolar) microdomains and one bulk cytosolic
domain was created using published information on the location of beta(1)ARs and
M(2)Rs, as well as the location of stimulatory (G(s)) and inhibitory (G(i))
G-proteins, adenylyl cyclase isoforms inhibited (AC5/6) and stimulated (AC4/7)
by G(i), and multiple phosphodiesterase isoforms (PDE2, PDE3, and PDE4). Results
obtained with the model indicate that: 1), bulk basal cAMP can be high (
approximately 1 microM) and only modestly stimulated by beta(1)AR activation (
approximately 2 microM), but caveolar cAMP varies in a range more appropriate
for regulation of protein kinase A ( approximately 100 nM to approximately 2
microM); 2), M(2)R activation strongly reduces the beta(1)AR-induced increases
in caveolar cAMP, with less effect on bulk cAMP; and 3), during weak beta(1)AR
stimulation, M(2)R activation not only reduces caveolar cAMP, but also produces
a rebound increase in caveolar cAMP following termination of M(2)R activity. We
conclude that compartmentation of cAMP can provide a quantitative explanation
for several aspects of cardiac signaling.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Iancu RV, Jones SW, Harvey RD. (2007) - version=1.0

The original CellML model was created by:
Geoffrey Nunns

[e-mail]
The University of Auckland
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