Abstract
We have constructed a three-dimensional reaction-diffusion model of
the mammalian cardiac calcium release unit. We analyzed effects of
diffusion coefficients, single channel current amplitude, density
of RyR channels, and reaction kinetics of ATP(2-) with Ca(2+) and
Mg(2+) ions on spatiotemporal concentration profiles of Ca(2+), Mg(2+),
and ATP(2-) in the dyadic cleft during Ca(2+) release. The model
revealed that Ca(2+) concentration gradients persist near RyRs in
the steady state. Even with low number of open RyRs, peak Ca(2+)
in the dyadic space reached values similar to estimates of luminal
Ca(2+) in approximately 1 ms, suggesting that during calcium release
the Ca(2+) gradient moves from the cisternal membrane towards the
boundary of the dyadic space with the cytosol. The released Ca(2+)
bound to ATP(2-), and thus substantially decreased ATP(2-) concentration
in the dyadic space. The released Ca(2+) could also replace Mg(2+)
in its complex with ATP(2-) during first milliseconds of release
if dissociation of MgATP was fast. The results suggest that concentration
changes of Ca(2+), Mg(2+), and ATP(2-) might be large and fast enough
to reduce dyadic RyR activity. Thus, under physiological conditions,
termination of calcium release may be facilitated by the synergic
effect of the construction and chemistry of mammalian cardiac dyads.
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