塑化劑泛指一些常用來軟化塑膠製品，進而使其彈性變佳的化學藥品。鄰苯二甲酸二(2-乙基己基)酯（Bis(2-ethylhexyl)-phthalate, DEHP）是塑化劑中最重要的一類，它以環境荷爾蒙（endocrine-disrupting chemicals）的功能而為人所知。在本研究中，我們嘗試探討DEHP和其他塑化劑包括鄰苯二甲酸二(2-丁氧基)乙酯（di(2-butoxyethyl)-phthalate, DBEP）和鄰苯二甲酸二(2-甲基乙二醇)酯（di(2-methylglycol)-phthalate, DMGP）對腦下垂體腫瘤GH3細胞中鉀離子電流的作用。細胞膜片箝制技術（patch-clamp technique）被用於偵測塑化劑在GH3細胞中的電生理效用。我們將GH3細胞浸於高鉀離子、去鈣離子的溶液中，以過極化電壓誘導erg鉀離子電流（ether-à-go–go-related-gene (erg) K+ current），並加入不同塑化劑以測量其效用。結果顯示，在GH3細胞中DEHP使erg鉀離子電流振幅減少並呈現濃度依賴性，其半數抑制濃度為16.3 μM。其次，DEHP使erg鉀離子電流的激活曲線往去極化電位平移約10mV，然而卻對其失活速率沒有顯著影響。濃度30 μM的DBEP對erg鉀離子電流缺乏效果，而同濃度的DMGP有微量抑制作用。此外，我們也測量DEHP對其他類型的鉀離子電流是否有效。在以inside-out模式記錄電流時，加入DEHP (30 μM)使巨型電導鈣離子活化鉀離子通道（large-conductance Ca2+-activated K+ channels）的活性有些許降低。30 μM的DEHP使GH3細胞中自發性動作電位的頻率增加；然而在以KCNH2 siRNA轉染的GH3細胞中，同濃度的DEHP對自發性動作電位的發射速率並沒有作用。本研究的結果顯示DEHP與其結構相似物的電生理作用。若在體內也有相似的發現，則可能說明這些物質是經此來調節內分泌或神經內分泌細胞的功能活性。

Phthalates are a class of chemicals often used as plasticizers because they can soften plastics to become more flexible. Bis(2-ethylhexyl)-phthalate (DEHP), an important phthalate, is recognized to be an endocrine-disrupting chemical. In this study , we attempted to evaluate the possible effects of DEHP and other phthalates, including di(2-butoxyethyl)-phthalate (DBEP) and di(2-methylglycol)-phthalate (DMGP), on ionic currents and membrane potential in pituitary tumor (GH3) cells. The patch-clamp technique was applied to investigate the electrophysiological effects of phthalates in these cells. GH3 cells were bathed in high K+ , Ca2+-free solution to induce the hyperpolarization-elicited K+ currents which were identified as ether-à-go–go-related-gene (erg) K+ current (IK(erg)). These cells were then treated with various phthalates to evaluate their effects on IK(erg). During cell exposure to DEHP, the amplitudes of IK(erg) in GH3 cells were significantly reduced in a concentration dependent manner with an IC50 value at 16.3 μM. Addition of DEHP also induced the activation curve of IK(erg) to shift toward depolarized potential by about 10mV; however, no significant change in the deactivation rate of IK(erg) was demonstrated in the presence of this agent. DBEP (30 μM) had minimal effect on IK(erg) while DMGP (30 μM) slightly suppressed it. Moreover, the effects of DEHP on other types of K+ currents were investigated. In inside-out current recordings, the activity of large-conductance Ca2+-activated K+ channels were slightly reduced as DEHP (30 μM) applied to the bath. In GH3 cells, DEHP (30 μM) increased the frequency of spontaneous action potentials (APs). However, DEHP had no effects on firing rate of APs at the same concentration in KCNH2 siRNA transfected GH3 cells. These results in this study indicated the effects of DEHP and other structurally similar compounds may contribute to regulation of the functional activity in endocrine or neuroendocrine cells if similar findings occur in vivo.

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