Cyclosporin A and deltamethrin block the downregulation of Nav1.8 sodium channels expressed in Xenopus oocytes
Cyclosporin A and deltamethrin block the downregulation of Nav1.8 sodium channels expressed in Xenopus oocytes
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DOI：
10.1016/j.neulet.2004.06.040
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发表时间：
2004-09-09
影响因子：
2.5
通讯作者：
Soderlund, DM
中科院分区：
文献类型：
--
作者：
Choi, JS;Soderlund, DM
在感觉神经元中表达的Na(v)1.8钠通道异构体与疼痛反应有关，已知在激活蛋白激酶a的药物作用下，非洲爪蟾卵母细胞中表达的Na(v)1.8通道表现出自发下调。因此，在30分钟的记录周期结束时，钠电流的峰值幅度减少到记录开始时的58%，而表达通道的性质没有变化。给卵母细胞灌注环孢素A或溴氰菊酯（被认为是蛋白磷酸酶钙调磷酸酶的诊断抑制剂），在10 muM时阻断自发下调。这些结果确定内源性钙调神经磷酸酶是卵母细胞Na(v)1.8钠通道下调的介质。环孢素a等钙调磷酸酶抑制剂的使用为卵母细胞中Na(v)1.8钠通道的表达提供了一种有效的稳定手段，可用于功能和药理学研究。2004爱思唯尔爱尔兰有限公司版权所有。
The Na(v)1.8 sodium channel isoform, expressed in sensory neurons and implicated in pain responses, is known to be upregulated in Xenopus oocytes by agents that activate protein kinase A. In the absence of exogenous modulators, Na(v)1.8 channels expressed in oocytes exhibited spontaneous downregulation, so that the amplitudes of peak sodium currents at the end of a 30-min recording period were reduced to 58% of those at the outset of recording with no change in the properties of the expressed channels. Perfusion of oocytes with either cyclosporin A or deltamethrin, considered to be diagnostic inhibitors of the protein phosphatase calcineurin, at 10 muM blocked spontaneous downregulation. These results identify endogenous calcineurin as the mediator of Na(v)1.8 sodium channel downregulation in oocytes. The use of a calcineurin inhibitor such as cyclosporin A provides an effective means of stabilizing the expression of Na(v)1.8 sodium channels in oocytes for functional and pharmacological studies. (C) 2004 Elsevier Ireland Ltd. All rights reserved.