Law of mass action, detailed balance, and the modeling of calcium puffs.

Using deterministic-stochastic simulations we show that for intracellular calcium puffs the mixing assumption for reactants does not hold within clusters of receptor channels. Consequently, the law of mass action does not apply and useful definitions of averaged calcium concentrations in the cluster are not obvious. Effective reaction kinetics can be derived, however, by separating concentrations for self-coupling of channels and coupling to different channels, thus eliminating detailed balance in the reaction scheme. A minimal Markovian model can be inferred, describing well calcium puffs in neuronal cells and allowing insight into the functioning of calcium puffs.