Efficient Approximations for Stationary Single-Channel Ca2+ Nanodomains across Length Scales
Efficient Approximations for Stationary Single-Channel Ca2+ Nanodomains across Length Scales
复制标题
跨长度尺度的固定单通道 Ca2 纳米域的有效近似
DOI：
10.1016/j.bpj.2020.06.038
复制
发表时间：
2020
影响因子：
3.4
通讯作者：
Matveev, Victor
中科院分区：
文献类型：
--
作者：
Chen, Yinbo;Muratov, Cyrill B.;Matveev, Victor
我们考虑在具有1：1 Ca2+结合的单个移动的Ca2+缓冲液存在下，描述单通道Ca2+纳米结构域的点Ca2+源附近的Ca2+浓度的固定解。我们提出了计算效率的近似估计稳定的单通道Ca2+纳米畴在参数空间的广泛区域具有很高的精度。所提出的近似有一个功能的形式，结合合理的和指数的功能，这是类似于众所周知的过量缓冲近似和线性近似，但参数估计使用两个新的，据我们所知，方法。其中一种方法涉及自由缓冲液浓度的短程泰勒级数和其长程渐近级数之间的内插，这些级数与通道距离的倒数幂有关。虽然这种方法已经被用来找到Padé（有理函数）逼近单通道Ca2+和缓冲液浓度，扩展这种方法的插值结合指数和有理函数提高了相关参数空间的一个重要部分的准确性。第二种方法是基于变分方法，并涉及一个适当的功能相对于所选择的近似参数的全局最小化。一个广泛的参数敏感性分析，比较这两种方法与以前开发的近似。除了增加的准确性，这些近似的力量是，他们可以扩展到更现实的缓冲液与多个结合位点的特点是合作的钙离子结合，如钙调蛋白和钙视蛋白。
We consider the stationary solution for the Ca2+concentration near a point Ca2+source describing a single-channel Ca2+nanodomain in the presence of a single mobile Ca2+buffer with 1:1 Ca2+binding. We present computationally efficient approximants that estimate stationary single-channel Ca2+nanodomains with great accuracy in broad regions of parameter space. The presented approximants have a functional form that combines rational and exponential functions, which is similar to that of the well-known excess buffer approximation and the linear approximation but with parameters estimated using two novel, to our knowledge, methods. One of the methods involves interpolation between the short-range Taylor series of the free buffer concentration and its long-range asymptotic series in inverse powers of distance from the channel. Although this method has already been used to find Padé (rational-function) approximants to single-channel Ca2+and buffer concentrations, extending this method to interpolants combining exponential and rational functions improves accuracy in a significant fraction of the relevant parameter space. A second method is based on the variational approach and involves a global minimization of an appropriate functional with respect to parameters of the chosen approximations. An extensive parameter-sensitivity analysis is presented, comparing these two methods with previously developed approximants. Apart from increased accuracy, the strength of these approximants is that they can be extended to more realistic buffers with multiple binding sites characterized by cooperative Ca2+binding, such as calmodulin and calretinin.