視丘下核神經元上回返性鈉離子電流生物物理特性之探討

The Biophysical Properties of Resurgent Sodium Current in Subthalamic Nucleus Neurons

周書民(Shu-Min Chou)

指導教授 ： 郭鐘金

國立臺灣大學/醫學院/生理學研究所/碩士(2012年)

https://doi.org/10.6342/NTU.2012.02906

摘要

神經的可興奮性在神經系統的激發特性上可說是相當重要的機制之一，而此一特性則與細胞膜上所表現的各種離子通道息息相關。在這眾多的離子通道之中，鈉離子通道所扮演的角色尤其顯著。近來的研究發現，有別於傳統認知上所定義的不活化路徑，回返性鈉離子電流經由一種受細胞內生性物質所誘發的路徑完成去活化過程，而此一機制提供了額外的閾下電流，進而促成了神經細胞去極化的產生。Raman和Bean在2001提出了一個模式圖，透過此一內生性物質的概念來闡述回返性鈉離子電流的形成機制。雖然，此一模式圖替這種在鈉離子通道不活化後依然產生的漏電現象提出了解釋，卻無法給與回返性電流發生之分子機制一個周延的說明，更多鈉離子通道相關的分子特性也依然有待釐清。在本論文中，我們將焦點著重於視丘下核的神經細胞上。此一神經核區與基底核在功能運作上息息相關，並且已被發現有回返性鈉離子電流的表現。為了瞭解回返性鈉離子電流的電生理特性，實驗中透過改變去極化與再極化的電位來觀察回返性鈉離子電流受電位變化調控的狀態。進一步藉由改變去極化的間期，觀察慢速不活化對於回返性鈉離子電流的影響。同時，透過不同電位下回返性電流的衰退常數，配合鈉電流回復曲線等來推測通道開啟態與抑制態之間的速率常數關係。此外，我們也探討了胞外多價陽離子對於回返性鈉電流的抑制作用，發現此一作用要遠比對於暫時性鈉電流(在前置去極化時見到之鈉電流)之抑制來得顯著。我們因此提出，回返性鈉電流應牽涉到一更大格局之鈉離子通道型態變化。此一變化應至少含括另一個不同於傳統活化態(較傳統開啟狀態不易活化)的開啟狀態，而非僅只由不同於通道不活化之阻塞作用所造成。

關鍵字

鈉離子通道 ； 回返性鈉離子電流 ； 視丘下核 ； 鎘離子 ； 鑭離子

並列摘要

Excitability is important for the firing properties of nervous system and is determined by the expression of different types of ion channels on the cell membrane. The sodium channels especially play a crucial role in membrane excitability. Recent studies indicate that an endogenous particle could evoke a so-called resurgent sodium current (I NaR) with a pore blocking mechanism different from classical inactivation and thus generate sodium current during the repolarization phase following depolarization of neurons. Although this model explained the occurrence of sodium current during the repolarization phase, it seemed to be less adequate in the interpretation of some major aspects of I NaR. In this study, we focus on subthalamic nucleus neurons which are functionally in close association with basal ganglia and consistently show I NaR . Membrane potential was stepped to different voltages and the result reflected that I NaR is dependent on not only the voltage of the repolarization phase but also the voltage and duration of the preceding depolarization phase. These findings are not completely compatible with the current model proposed by Raman and Bean. Furthermore, the extracellular Lanthanum and Cadmium were found to affect I NaR more than I NaT (the transient sodium current elicited in the preceding depolarization phase). We maintain that the sodium channel necessarily contains more than one open state for the molecular mechanism underlying the genesis of I NaR and a new model is forwarded accordingly.

並列關鍵字

Sodium channel ； Sodium resurgent current ； Subthalamic nucleus ； Cadmium ； Lanthanum

參考文獻

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