The dynamics of intracellular Ca²⁺ is driven by random events called Ca²⁺ puﬀs, in which Ca²⁺ is liberated from intracellular stores. We show that the emergence of Ca²⁺ puﬀs can be mapped to an escape process. The mean ﬁrst passage times that correspond to the stochastic fraction of puﬀ periods are computed from a novel master equation and two Fokker-Planck equations. Our results demonstrate that the mathematical modeling of Ca²⁺ puﬀs has to account for the discrete character of the Ca²⁺ release sites and does not permit a continuous description of the number of \ud open channels
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