Hodgkin-Huxley (HH) 模型對於電流生理學的發展有著深遠的影響。它能精確地模擬離子通道的變化。然而，隨著多年來的反覆驗證，研究人員發現HH模型亦有其局限性和不足之處。有見及此，本論文提出一個建基於變形動力學的模型，藉此以更深入的物理層面解釋Hodgkin與Huxley的實驗數據。新的模型為鉀與鈉離子通道建立了新的電導方程。在這模型的詮釋下，HH模型的鉀離子通道電導方程[附圖] 被[附圖]取代，而HH模型的鈉離子通道電導方程 [附圖] 則被 [附圖] 取而代之。縱使 n(t), m(t)和 h(t)在兩個模型中被授予不同的物理意義，但它們均是一階微分方程。此論文詳細闡述模型的建立過程及參數的推導，並論證它能準確地描繪Hodgkin與Huxley對於烏賊巨軸突的實驗數據。模型參數經由遺傳演算法優化後，新的模型不僅能夠準確描述離子通道的電導變化，還能闡述Cole-Moore shift現象。在相同強度的去極化刺激和溫度下，新的模型比HH模型能接近地模擬膜動作電位的實驗數據。 / Hodgkin-Huxley (HH) model has a profound influence on the development of electrophysiology. It is capable of modeling the transient responses of voltage-gated ion channels precisely. Nevertheless, limitations and deficiencies of the model were found as researchers conducted subsequent experiments. In this regard, a new model based on deformation kinetic has been put forth to help explaining the HH experimental data with a deeper level of physical insight. Under the proposed model, the famous HH equation [with formula] for the description of potassium conductance was replaced by [with formula] and the HH sodium conductance equation [with formula] was substituted by [with formula]. Meanwhile, n(t), m(t) and h(t) are still first order differential equations as the HH case. This thesis contributes to illustrate the capability of the new model in approximating HH’s experimental data on squids’ giant axons. Detailed derivation of the new model and identification of the parametric functions are summarized in this report. A customized genetic algorithm was utilized to optimize the model parameters. After fine tuning the new model, we are able to describe the conductance behaviors of voltage-gated ion channels closely, and manage to account for the Cole-Moore shift phenomenon. Under identical initial depolarizing stimuli and temperature as stated in HH’s experiments, close approximations of membrane action potential can also be obtained by the new model. / Detailed summary in vernacular field only. / Yu, Cheuk Him Derek. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 69-70). / Abstracts also in Chinese. / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Overview of Electrophysiological Models --- p.4 / Chapter 1.2 --- The Hodgkin-Huxley Membrane Current Model --- p.4 / Chapter 1.2.1 --- Hodgkin-Huxley Potassium Channel --- p.6 / Chapter 1.2.2 --- Hodgkin-Huxley Sodium Channel --- p.8 / Chapter 1.3 --- Proliferation of the Deformation Kinetic Based Model --- p.10 / Chapter 1.4 --- Thesis Outline --- p.12 / Chapter 2 --- The Deformation Kinetic Based Model --- p.13 / Chapter 2.1 --- The Molecular Theory --- p.13 / Chapter 2.1.1 --- Application of Deformation Kinetics --- p.13 / Chapter 2.1.2 --- The Energy Function E{U+2093} (q) --- p.14 / Chapter 2.1.3 --- The Population Distribution Function P{U+2093} (N,t) --- p.17 / Chapter 2.1.4 --- Conductance Model for Voltage-gated Ion Channels --- p.18 / Chapter 2.2 --- The Approximate Solutions --- p.19 / Chapter 2.2.1 --- Approximation of the General Solution for G{U+2093} (N) --- p.19 / Chapter 2.2.2 --- Approximation of the General Solution for P{U+2093} (N,t) --- p.19 / Chapter 2.2.3 --- The Approximate Solution for Molecular g{U+2093} (t) --- p.23 / Chapter 2.2.4 --- A Convenient Form of the Approximate Solutions --- p.24 / Chapter 2.3 --- Chapter Summary --- p.25 / Chapter 3 --- Voltage-gated Ion Channel Modeling --- p.27 / Chapter 3.1 --- Voltage-gated Potassium Channel Modeling --- p.27 / Chapter 3.2 --- Voltage-gated Sodium Channel Modeling --- p.29 / Chapter 3.3 --- Chapter Summary --- p.31 / Chapter 4 --- The Parametric Functions --- p.32 / Chapter 4.1 --- The Curve Fitting References - HH Experimental Data --- p.32 / Chapter 4.2 --- Curve Fitting through Genetic Algorithm --- p.34 / Chapter 4.3 --- Functional Approximations w.r.t. HH Experimental Data --- p.37 / Chapter 4.3.1 --- Parametric Functions for Voltage-gated Potassium Channel --- p.37 / Chapter 4.3.2 --- Parametric Functions for Voltage-gated Sodium Channel --- p.39 / Chapter 4.4 --- Chapter Summary --- p.46 / Chapter 5 --- The Tracing Results --- p.47 / Chapter 5.1 --- Voltage Clamp Tracings --- p.47 / Chapter 5.1.1 --- Potassium Conductance Tracings --- p.48 / Chapter 5.1.2 --- Sodium Conductance Tracings --- p.49 / Chapter 5.2 --- Membrane Action Potential Tracings --- p.54 / Chapter 5.3 --- Propagated Action Potential Tracings --- p.56 / Chapter 5.4 --- Chapter Summary --- p.59 / Chapter 6? --- The Cole-Moore Shift Phenomenon --- p.60 / Chapter 6.1 --- Cole-Moore shift Phenomenon of Voltage-gated Potassium Channel --- p.61 / Chapter 6.2 --- Cole-Moore Shift Phenomenon of Voltage-gated Sodium Channel --- p.62 / Chapter 6.3 --- Chapter Summary --- p.64 / Chapter 7 --- Discussions --- p.65 / Conclusion --- p.67 / Future Works --- p.68 / References --- p.69 / Chapter Appendix I --- Hodgkin-Huxley’s Analysis of Voltage-gated Channels’ Voltage Clamp Data / Chapter (a) --- HH’s Analysis of Potassium Conductance Change in Voltage Clamp Experiments --- p.71 / Chapter (b) --- HH’s Analysis of Sodium Conductance Change in Voltage Clamp Experiments --- p.71 / Chapter Appendix II --- Numerical Estimations of Hodgkin-Huxley’s Experimental Data / Chapter (a) --- Numerical Estimations of Podium Conductance Change in Voltage Clamp Experiments for HH axon 17 --- p.72 / Chapter (b) --- Numerical Estimations of Sodium Conductance Change in Voltage Clamp Experiments for HH axon 17 --- p.73 / Chapter (c) --- Numerical Estimations of Membrane Action Potential with Different Initial Depolarizations for HH axon 17 --- p.74 / Chapter Appendix III --- Verification of the Replica of HH Model’s Simulations Results / Chapter (a) --- Comparison between HH Membrane Action Potential and Its Replica --- p.75 / Chapter (b) --- Comparison between HH Propagated Action Potential and Its Replica --- p.76
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_328757 |
| Date | January 2012 |
| Contributors | Yu, Cheuk Him Derek., Chinese University of Hong Kong Graduate School. Division of Mechanical and Automation Engineering. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, bibliography |
| Format | electronic resource, electronic resource, remote, 1 online resource (xi, 76 leaves) : ill. (some col.) |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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