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 ATP2− with Ca2+ and Mg2+ ions on spatiotemporal concentration profiles of Ca2+, Mg2+, and ATP2− in the dyadic cleft during Ca2+ release. The model revealed that Ca2+ concentration gradients persist near RyRs in the steady state. Even with low number of open RyRs, peak [Ca2+] in the dyadic space reached values similar to estimates of luminal [Ca2+] in ∼1 ms, suggesting that during calcium release the Ca2+ gradient moves from the cisternal membrane towards the boundary of the dyadic space with the cytosol. The released Ca2+ bound to ATP2−, and thus substantially decreased ATP2− concentration in the dyadic space. The released Ca2+ could also replace Mg2+ in its complex with ATP2− during first milliseconds of release if dissociation of MgATP was fast. The results suggest that concentration changes of Ca2+, Mg2+, and ATP2− 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.