Mapping Interpuff Interval Distribution to the Properties of Inositol Trisphosphate Receptors

Tightly clustered inositol trisphosphate receptors (IPRs) control localized Ca liberation from the endoplasmic reticulum to generate repetitive Ca puffs. Distributions of the interpuff interval (IPI), i.e., the waiting time between successive puffs, are found to be well characterized by a probability density function involving only two parameters, λ and ξ, which represent the basal rate of puff generation and the recovery rate from refractoriness, respectively. However, how the two parameters depend on the kinetic parameters of single IPRs in a cluster is still unclear. In this article, using a stochastic puff model and a single-channel data-based IPR model, we establish the dependencies of λ and ξ on two important IPR model parameters, IP concentration ([IP]) and the recovery rate from Ca inhibition (r). By varying [IP] and r in physiologically plausible ranges, we find that the ξ-λ plane is comprised of only two disjoint regions, a biologically impermissible region and a region where each parameter set (ξ, λ) can be caused by using two different combinations of [IP] and r. The two combinations utilize very different mechanisms to maintain the same IPI distribution, and the mechanistic difference provides a way of identifying IPR kinetic parameters by observing properties of the IPI.