A kinetic analysis of calcium-triggered exocytosis

Although the relationship between exocytosis and calcium is fundamental bot h to synaptic and nonneuronal secretory function, analysis is problematic b ecause of the temporal and spatial properties of calcium, and the fact that vesicle transport, priming, retrieval, and recycling are coupled. By analy zing the kinetics of sea urchin egg secretory vesicle exocytosis in vitro, the final steps of exocytosis are resolved. These steps are modeled as a th ree-state system: activated, committed, and fused, where interstate transit ions are given by the probabilities that an active fusion complex commits ( alpha) and that a committed fusion complex results in fusion, p. The number of committed complexes per vesicle docking site is Poisson distributed wit h mean (n) over bar. Experimentally, p arid (n) over bar increase with incr easing calcium, whereas alpha and the p/(n) over bar ratio remain constant, reducing the kinetic description to only one calcium-dependent, controllin g variable, n. On average, the calcium dependence of the maximum rate (R-ma x) and the time to reach R-max (T-peak) are described by the calcium depend ence of (n) over bar. Thus, the nonlinear relationship between the free cal cium concentration and the rate of exocytosis can be explained solely by th e calcium dependence of the distribution of fusion complexes at vesicle doc king sites.