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Mapping interpuff interval distribution to the properties of inositol trisphosphate receptors

Item Type:Article
Title:Mapping interpuff interval distribution to the properties of inositol trisphosphate receptors
Creators Name:Cao, P. and Falcke, M. and Sneyd, J.
Abstract:Tightly clustered inositol trisphosphate receptors (IP3Rs) control localized Ca2+ liberation from the endoplasmic reticulum to generate repetitive Ca2+ 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, lambda and xi, 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 IP3Rs in a cluster is still unclear. In this article, using a stochastic puff model and a single-channel data-based IP3R model, we establish the dependencies of lambda and xi on two important IP3R model parameters, IP3 concentration ([IP3]) and the recovery rate from Ca2+ inhibition (rlow). By varying [IP3] and rlow in physiologically plausible ranges, we find that the xi-lambda plane is comprised of only two disjoint regions, a biologically impermissible region and a region where each parameter set (xi, lambda) can be caused by using two different combinations of [IP3] and rlow. The two combinations utilize very different mechanisms to maintain the same IPI distribution, and the mechanistic difference provides a way of identifying IP3R kinetic parameters by observing properties of the IPI.
Keywords:Calcium, Divalent Cations, Inositol 1,4,5-Trisphosphate, Inositol 1,4,5-Trisphosphate Receptors, Kinetics, Markov Chains, Molecular Models
Source:Biophysical Journal
ISSN:0006-3495
Publisher:Biophysical Society (U.S.A.)
Volume:112
Number:10
Page Range:2138-2146
Date:23 May 2017
Official Publication:https://doi.org/10.1016/j.bpj.2017.03.019
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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