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題 名 | Contribution of Non-Inactivating Na⁺ Current Induced by Oxidizing Agents to the Firing Behavior of Neuronal Action Potentials: Experimental and Theoretical Studies from NG108-15 Neuronal Cells |
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作 者 | Wu, Sheng-nan; Lo, Yi-ching; Shen, Ai-yu; Chen, Bing-shuo; | 書刊名 | 中國生理學雜誌 |
卷 期 | 54:1 2011.02[民100.02] |
頁 次 | 頁19-29 |
分類號 | 398.2 |
關鍵詞 | t-butyl hydroperoxide; Na⁺ current; Non-inactivating Na⁺ current; Action potential; Computer simulations; |
語 文 | 英文(English) |
英文摘要 | The effects of chemical injury with oxidizing agents on voltage-gated Na+ current (INa) in differentiated NG108-15 neuronal cells were investigated in this study. In whole-cell patch-clamp recordings, the challenge of these cells with t-butyl hydroperoxide (t-BHP; 1 mM) decreased the peak amplitude of INa with no modification in the current-voltage relationship. It caused a slowing of current inactivation, although there was no alteration in the activation time course of INa. Cell exposure to t-BHP also increased a non-inactivating INa (INa(NI)) elicited by long-lasting ramp pulses. The t-BHP-induced increase of INa(NI) was reversed by a further application of riluzole (10 μM) or oxcarbazepine (10 μM). When INa was elicited by simulated waveforms of action potentials (APs), during exposure to t-BHP, the amplitude of this inward current was diminished, accompanied by a reduction in inactivation/deactivation rate and an increase in current fluctuations. Under current-clamp recordings, addition of t-BHP (0.3 mM) enhanced AP firing in combination with clustering-like activity and sub-threshold membrane oscillations. In the simulation study, when the fraction of non-inactivating NaV channels was elevated, the simulated window component of INa in response to a long-lasting ramp pulse was reduced; however, the persistent INa was markedly enhanced. Moreover, when simulated firing of APs was generated from a modeled neuron, changes of AP firing caused by the increased fraction of non-inactivating NaV channels used to mimic the t-BHP actions were similar to the experimental observations. Taken together, it is anticipated that the effects of oxidizing agents on INa(NI) could be an important m |
本系統中英文摘要資訊取自各篇刊載內容。