Fig. 5: Modelling vesicular release for single and dual clamp models in response to bursts of action potentials in MFB terminals.

a Top, VCell-computed [Ca²⁺](t) transient approximating Ca²⁺ dynamics at vesicular release sites in MFB terminals in response to a 10 × 100 Hz AP train (see ref. ²⁸). Bottom, time course of corresponding vesicular release rates for the benchmark allosteric model and the three fusion clamp architectures. b Top, expected numbers of vesicles exocytosed at a single release site, \({n}_{T}(N)\), for each AP of the train, \(N\). Bottom, paired-pulse ratio: release efficacy at each AP normalised to release efficacy at the first AP, \({n}_{T}(N)/{n}_{T}(1)\). c Top, [Ca²⁺]_residual after the 10 × 100 Hz AP train, corresponding to the dashed box in (a). Bottom, corresponding cumulative asynchronous releases per release site, \({n}_{{{{{\rm{Async}}}}}}\), for the three fusion clamp architectures and the benchmark allosteric model. Data points represent mean values. For each [Ca²⁺](t) transient and fusion clamp architecture at least N = 100,000 stochastic simulations were performed with at least 6000 vesicular fusion events recorded during the AP train.