Abstract
A tight coupling between ionic currents, intracellular Ca2+ homeostasis,
cytosolic ADP and deltaG of ATP hydrolysis underlies the regulation
of cardiac cell function. As more experimental detail on the biochemistry
and biophysics of these complex processes and their interactions
accumulates, the intuitive interpretation of the new findings becomes
increasingly impractical. For this reason we developed detailed biophysical
model that couples Ca2+ signaling, cell electrophysiology and bioenergetics
with the main interactions between phosphorylated species (ATP, ADP,
AMP, PCr, Cr, P(i)) and Lewis cytosolic acids (Na+, K+, Mg2+, H+).
The results indicate that the increase in free cytosolic Mg2+ (0.2-5
mM) systematically shortens the action potential duration. The analysis
suggests that that under physiological conditions a pH decrease accompanied
by a free Mg2+ increase tends to counteract an ADP increase due
to PCr depletion. The model reproduces qualitatively a sequence of
events that correlates well with the experimental data.
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