Modelling of some potential effects of lumenal Ca2+ binding on the kinetics of Ca2+ release from the endoplasmic...

The time course of Ca2+ release from intracellular stores during a prolonged exposure to a constant concentration of inositol 1,4,5-trisphosphate does not follow a single exponential but presents a progressive slowing down of the relative rate of efflux. Among the many factors that may contribute to this phenomenon, the possible contribution of lumenal Ca2+ buffering has been largely neglected. However, since the efflux rate depends on the free Ca2+ concentration whereas the total Ca2+ content is mainly determined by bound Ca2+, simple Ca2+ efflux kinetics can be expected only if there is a linear relation between free Ca2+ and bound Ca2+. Although little is known on lumenal Ca2+ binding, reasonable assumptions predict that the ratio of (Ca2+ bound)/(Ca2+ free) may decrease with increasing free Ca2+ concentrations, implying a continuously decreasing rate coefficient, as is experimentally observed. Simulated Ca2+ release curves show significant deviations from a single exponential if high-affinity binding sites are present in addition to low-affinity sites. Although this simple model does not predict several of the experimentally observed properties, it is concluded that a full understanding of Ca2+ release kinetics requires more detailed information on lumenal Ca2+ buffering within Ca2+ stores.