a numerical approach to ion channel modelling using whole-cell voltage-clamp recordings and a genetic algorithm离子通道的数值方法模拟使用全细胞电压钳记录和遗传算法.pdfVIP

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a numerical approach to ion channel modelling using whole-cell voltage-clamp recordings and a genetic algorithm离子通道的数值方法模拟使用全细胞电压钳记录和遗传算法.pdf

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a numerical approach to ion channel modelling using whole-cell voltage-clamp recordings and a genetic algorithm离子通道的数值方法模拟使用全细胞电压钳记录和遗传算法

A Numerical Approach to Ion Channel Modelling Using Whole-Cell Voltage-Clamp Recordings and a Genetic Algorithm Meron Gurkiewicz1,2, Alon Korngreen1,2* 1 The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel 2 The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar- Ilan University, Ramat-Gan, Israel The activity of trans-membrane proteins such as ion channels is the essence of neuronal transmission. The currently most accurate method for determining ion channel kinetic mechanisms is single-channel recording and analysis. Yet, the limitations and complexities in interpreting single-channel recordings discourage many physiologists from using them. Here we show that a genetic search algorithm in combination with a gradient descent algorithm can be used to fit whole-cell voltage-clamp data to kinetic models with a high degree of accuracy. Previously, ion channel stimulation traces were analyzed one at a time, the results of these analyses being combined to produce a picture of channel kinetics. Here the entire set of traces from all stimulation protocols are analysed simultaneously. The algorithm was initially tested on simulated current traces produced by several Hodgkin-Huxley–like and Markov chain models of voltage-gated potassium and sodium channels. Currents were also produced by simulating levels of noise expected from actual patch recordings. Finally, the algorithm was used for finding the kinetic parameters of several voltage- gated sodium and potassium channels models by matching its results to data recorded from layer 5 pyramidal neurons of the rat cortex in the nucleated outside-out patch configuration. The minimization scheme gives electrophysiologists a tool for reproducing and simulating voltage-gated ion channel kinetics at the cellular level. Citation: Gurkiewicz M, Korngreen A (2007) A numerical approach to ion channel modelling us