文章基本信息

标题：Computational Methods for Estimating Molecular System from Membrane Potential Recordings in Nerve Growth Cone
本地全文：下载
作者：Tatsuya Yamada ; Makoto Nishiyama ; Shigeyuki Oba 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2018
卷号：8
期号：1
页码：4559
DOI：10.1038/s41598-018-22506-3
语种：English
出版社：Springer Nature
摘要：Biological cells express intracellular biomolecular information to the extracellular environment as various physical responses. We show a novel computational approach to estimate intracellular biomolecular pathways from growth cone electrophysiological responses. Previously, it was shown that cGMP signaling regulates membrane potential (MP) shifts that control the growth cone turning direction during neuronal development. We present here an integrated deterministic mathematical model and Bayesian reversed-engineering framework that enables estimation of the molecular signaling pathway from electrical recordings and considers both the system uncertainty and cell-to-cell variability. Our computational method selects the most plausible molecular pathway from multiple candidates while satisfying model simplicity and considering all possible parameter ranges. The model quantitatively reproduces MP shifts depending on cGMP levels and MP variability potential in different experimental conditions. Lastly, our model predicts that chloride channel inhibition by cGMP-dependent protein kinase (PKG) is essential in the core system for regulation of the MP shifts.