Spatial and temporal Ca2+, Mg2+, and ATP2- dynamics in cardiac dyads during calcium release.
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.
Valent
Ivan
I
Department of Physical and Theoretical Chemistry, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia.
Zahradníková
Alexandra
A
Pavelková
Jana
J
Zahradník
Ivan
I
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling; D003198:Computer Simulation; D003600:Cytosol / Q000378:metabolism; D004058:Diffusion; D006801:Humans; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism*; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000378:metabolism*; D012107:Research Design; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D019837:Ryanodine Receptor Calcium Release Channel; D000255:Adenosine Triphosphate; D008274:Magnesium