A simple sequential-binding model for calcium puffs.

Calcium puffs describe the transient release of Ca(2+) ions into the cytosol, through small clusters of 1,4,5-inositol triphosphate (IP(3)) receptors, present on internal stores such as the endoplasmic reticulum. Statistical properties of puffs, such as puff amplitudes and durations, have been well characterized experimentally. We model calcium puffs using a simple, sequential-binding model for the IP(3) receptor in conjunction with a computationally inexpensive point-source approximation. We follow two different protocols, a sequential protocol and a renewal protocol. In the sequential protocol, puffs are generated successively by the same cluster; in the renewal protocol, the system is reset after each puff. In both cases for a single set of parameters our results are in excellent agreement with experimental results for puff amplitudes and durations but indicate puff-to-puff correlations for the sequential protocol, consistent with recent experimental findings [H. J. Rose, S. Dargan, J. W. Shuai, and I. Parker, Biophys. J. 91, 4024 (2006)]. The model is then used to test the consistency of the hypothesized steep Ca(2+) gradients around single channels with the experimentally observed features of puff durations and amplitudes. A three-dimensional implementation of our point-source model suggests that a peak Ca(2+) concentration of the order of 10 muM at the cluster site (not channel) is consistent with the statistical features of observed calcium puffs.