(A–E) Effect on release latencies (left) and peak release rates (right) when varying α (A), γ (B), [PI(4,5)P2] (C), f (D), and d (E). The best-fit values of each of the parameters were increased and decreased by a factor 2, 3, and 5. Varying α and γ leads to a change in β and δ so that the measured affinities for both Ca2+ and PI(4,5)P2 are still matched (van den Bogaart et al., 2012). (A) When varying α the release latency is mostly affected in the middle range of [Ca2+]i. The effect on the peak release rates is very small. (B) Varying γ has no effect on release latencies. The effect of varying γ on peak release is larger at high [Ca2+]i compared to low [Ca2+]i reflecting that at high [Ca2+]i PI(4,5)P2 binding limits dual binding formation. (C) Varying [PI(4,5)P2] has a large effect on the release latencies and peak release rates. The effect of varying [PI(4,5)P2] is much larger compared to varying γ, as changing [PI(4,5)P2] only affects the binding rate of PI(4,5)P2, whereas changing γ leads to an equal change in δ to match the published affinity values. Consequently, [PI(4,5)P2] affects the steady state distribution. (D) Varying f has a large effect on both release latency and fusion rate, as it directly impacts the effect of dual binding formation on SV fusion rates. (E) Varying the added delay, d, only shifts the release latencies linearly and does not affect the peak release rates. Experimental data points in these figures are replotted from Kochubey and Schneggenburger, 2011.