Matveev V
Department of Mathematical Sciences, New Jersey Institute of Technology, Newark, New Jersey.
Biophys J. 2016 Nov 1;111(9):2062-2074. doi: 10.1016/j.bpj.2016.09.019.
We consider the stationary solution for the Ca concentration near a point Ca source describing a single-channel Ca nanodomain, in the presence of a single mobile buffer with one-to-one Ca binding stoichiometry. Previously, a number of Ca nanodomains approximations have been developed, for instance the excess buffer approximation (EBA), the rapid buffering approximation (RBA), and the linear approximation (LIN), each valid for appropriate buffering conditions. Apart from providing a simple method of estimating Ca and buffer concentrations without resorting to computationally expensive numerical solution of reaction-diffusion equations, such approximations proved useful in revealing the dependence of nanodomain Ca distribution on crucial parameters such as buffer mobility and its Ca binding properties. In this study, we present a different form of analytic approximation, which is based on matching the short-range Taylor series of the nanodomain concentration with the long-range asymptotic series expressed in inverse powers of distance from channel location. Namely, we use a "dual" Padé rational function approximation to simultaneously match terms in the short- and the long-range series, and we show that this provides an accurate approximation to the nanodomain Ca and buffer concentrations. We compare this approximation with the previously obtained approximations and show that it yields a better estimate of the free buffer concentration for a wide range of buffering conditions. The drawback of our method is that it has a complex algebraic form for any order higher than the lowest bilinear order, and cannot be readily extended to multiple Ca channels. However, it may be possible to extend the Padé method to estimate Ca nanodomains in the presence of cooperative Ca buffers with two Ca binding sites, the case that existing methods do not address.
我们考虑在存在具有一对一钙结合化学计量的单个移动缓冲剂的情况下,描述单通道钙纳米域的钙源附近钙浓度的稳态解。此前,已经开发了许多钙纳米域近似方法,例如过量缓冲近似(EBA)、快速缓冲近似(RBA)和线性近似(LIN),每种方法在适当的缓冲条件下都是有效的。除了提供一种无需借助反应扩散方程的计算成本高昂的数值解来估计钙和缓冲剂浓度的简单方法外,这些近似方法在揭示纳米域钙分布对诸如缓冲剂迁移率及其钙结合特性等关键参数的依赖性方面也被证明是有用的。在本研究中,我们提出了一种不同形式的解析近似方法,该方法基于将纳米域浓度的短程泰勒级数与以距通道位置距离的倒数幂表示的长程渐近级数相匹配。具体而言,我们使用“对偶”帕德有理函数近似来同时匹配短程和长程级数中的项,并表明这为纳米域钙和缓冲剂浓度提供了准确的近似。我们将这种近似与先前获得的近似进行比较,并表明在广泛的缓冲条件下,它对游离缓冲剂浓度的估计更好。我们方法的缺点是,对于任何高于最低双线性阶数的阶数,它都具有复杂的代数形式,并且不能轻易扩展到多个钙通道。然而,有可能将帕德方法扩展到估计存在具有两个钙结合位点的协同钙缓冲剂时的钙纳米域,这是现有方法未涉及的情况。