Tefluthrin (Tef)是一種合成的第一型除蟲菊，它被用來控制許多種昆蟲的數量。由於全世界使用除蟲菊的用量增加，我們需要更加了解人類暴露在除蟲菊下的作用機制。過去許多研究指出Tef以及其結構相關的化合物會影響多種離子通道的活性。然而，Tef對於內分泌或神經內分泌細胞中離子電流的電生理特性卻很少被研究。因此，在這個研究中，將會探討Tef對於GH3以及GT1-7細胞的離子電流的作用機制。實驗中，我們發現在GH3細胞中給予10 M的Tef可以增加電壓依賴鈉離子電流的大小，並且伴隨著鈉離子電流的不活化以及去活化時間常數的增加。此外，Tef會使鈉離子電流的電流-電壓 (I-V)曲線往較負的電位偏移。此化合物也會增加持續性鈉離子電流的大小，並讓持續性鈉離子電流的I-V 曲線偏移到較負的電位。然而，Tef卻會減少L型電壓依賴鈣離子電流的大小。另外這個化合物會些微抑制向外的鉀離子電流，不過並不改變巨型電導鈣離子活化鉀離子通道的活性。在cell-attached voltage-clamp的實驗中，Tef會增加GH3和GT1-7細胞的自發性動作電流的大小以及頻率。之後我們利用從實驗獲得的參數建構出以Hodgkin-Huxley為基準的GH3細胞模型。將實驗中測得Tef對於離子電流的影響套用到細胞模型當中來模擬Tef對於GH3細胞的電活性改變。在模擬的情況中，我們發現Tef會增加自發性動作電位的頻率以及增加泌乳激素的分泌。總結而言，我們的研究顯示了Tef或其他除蟲菊可能透過對離子電流的影響而使活體中內分泌或神經內分泌細胞的功能受到改變。

Tefluthrin (Tef), a synthetic type-I pyrethroid, was used to control a wide range of insects. Since global use of pyrethroids has increased, a rise in acute pyrethroid exposures in humans demands a more complete understanding of their mechanism of actions. Previous studies showed that Tef and its structurally-related compounds affected the activity of different ion channels. However, no detailed electrophysiological characterization of the effects of Tef on ion currents in endocrine or neuroendocrine cells has been investigated. In this study, the mechanism of actions through which Tef interacts with ion currents was thus studied in GH3 cells and GT1-7 neurons. Application of Tef (10 M) enhanced the amplitude of voltage-gated Na+ currents (INa), accompanied by an increase in the time constants of inactivation and deactivation in GH3 cells. The current-voltage (I-V) relationship of INa was shifted to more negative potentials in the presence of this compound. It also increased the amplitude of persistent sodium current (INa,P), together with a negative shift of the I-V relationship. However, Tef reduced the amplitude of L-type Ca2+ current (ICa,L). This compound slightly inhibited K+ outward current (IK), but it did not alter the activity of large-conductance Ca2+-activated K+ (BKCa) channels. Under cell-attached voltage-clamp recordings, Tef increased amplitude and frequency of spontaneous action currents in GH3 and GT1-7 cells. A GH3 cell model was constructed using Hodgkin-Huxley parameters obtained from experiments. We incorporated the effects of Tef on ion currents to our model to simulate its effects on the electric activity of GH3 cells. The simulation indicates that Tef can increase the frequency of spontaneous action potentials and prolactin secretion level. Taken together, our study reveals that the effects of Tef or other pyrethroids on ion currents account for the mechanisms how they influence endocrine or neuroendocrine function in vivo.

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