应用免疫算法研究肌醇1,4,5-磷酸三酯受体通道模型参数分布特性

Parameter Distributions of Inositol 1,4,5-Trisphosphate Receptor Channel Model with the Immune Algorithm

肌醇1,4,5-磷酸三酯受体(inositol 1,4,5-trisphosphate receptor,IP3R)是内质网钙离子释放的重要通道,对细胞信号的传递至关重要。国内外已经提出一些IP3R通道模型,用来解释拟合IP3R通道膜片钳实验数据,其中的De Young-Keizer模型在数值模拟中应用最为广泛。随着人工免疫系统研究的迅速发展,人工免疫算法已经在多目标优化问题上取得了广泛应用。作者应用混合免疫多目标优化算法,根据爪蟾卵母细胞和草地夜蛾细胞核膜IP3R通道的开放概率、平均开放时间和平均闭合时间的动力学实验数据,对De Young-Keizer通道模型进行参数拟合,获得大量优化的拟合参数,从而得到通道模型参数分布图。通过对比两种细胞的拟合参数分布,指出这两种不同细胞IP3R通道的开关动力学差异,主要来源于抑制Ca2+结合时IP3结合位点和当IP3结合时抑制Ca2+结合位点的结合动力学不同。

The inositol 1,4,5-trisphosphate receptor （IP3R）, which is a Ca2＋-release channel in the endoplasmic reticulum, plays an important role in cellular signaling system. In recent years, several IP3R models have been proposed to fit the stationary data of patch clamp recordings. The De Young-Keizer model is one of the most widely applied IP3R models. With the rapid development of artificial immune system, the artificial immune algorithms have been widely applied to multi-objective optimization problems. In this paper, the authors applied the immune algorithm to fit the parameters in De Young-Keizer model according to the nuclear membrane experimental data of open probability, mean open time and mean closing time of the Xenopus oocyte and Spodoptera frugiperda Sf9 cells. By comparing the fitting parameter distributions of the two types of channels, it is indicated that the differences in the IPzR channel dynamics between the two types of cells are originated from the dynamic differences in the IP3 binding site when inhibitory Ca2＋ is bonded and the inhibitory Ca2＋ binding site when IP3 is bonded.