Cao Pengxing, Falcke Martin, Sneyd James
School of Mathematics and Statistics, The University of Melbourne, Melbourne, Victoria, Australia.
Mathematical Cell Physiology, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Biophys J. 2017 May 23;112(10):2138-2146. doi: 10.1016/j.bpj.2017.03.019.
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.
紧密聚集的肌醇三磷酸受体（IPRs）控制着从内质网局部释放钙离子，以产生重复性的钙瞬变。人们发现，钙瞬变间隔（IPI）（即连续两次钙瞬变之间的等待时间）的分布可以用一个仅涉及两个参数λ和ξ的概率密度函数很好地描述，这两个参数分别代表钙瞬变产生的基础速率和从不应期恢复的速率。然而，这两个参数如何依赖于簇中单个IPR的动力学参数仍不清楚。在本文中，我们使用一个随机钙瞬变模型和一个基于单通道数据的IPR模型，建立了λ和ξ与IPR模型的两个重要参数——肌醇三磷酸浓度（[IP]）和钙抑制恢复速率（r）之间的依赖关系。通过在生理合理范围内改变[IP]和r，我们发现ξ-λ平面仅由两个不相交的区域组成，一个是生物学上不允许的区域，另一个是每个参数集（ξ，λ）可以由[IP]和r的两种不同组合导致的区域。这两种组合利用非常不同的机制来维持相同的IPI分布，而这种机制上的差异提供了一种通过观察IPI的特性来识别IPR动力学参数的方法。
