Suppressive effects of nonsteroidal anti-inflammatory drugs diclofenac sodium, salicylate and indomethacin on delayed rectifier K+-channel currents in murine thymocytes
Suppressive effects of nonsteroidal anti-inflammatory drugs diclofenac sodium, salicylate and indomethacin on delayed rectifier K+-channel currents in murine thymocytes
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DOI：
10.3109/08923973.2012.666249
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发表时间：
2012-10-01
影响因子：
3.3
通讯作者：
Murata, Yoshimichi
中科院分区：
文献类型：
--
作者：
Kazama, Itsuro;Maruyama, Yoshio;Murata, Yoshimichi
淋巴细胞主要在其质膜上表达延迟整流K+通道（Kv1.3），并且该通道在淋巴细胞活化和增殖中起关键作用。非甾体类抗炎药（NSAIDs）是最常用的镇痛、解热药物，由于其具有免疫调节作用，因此会影响淋巴细胞通道电流。在本研究中，采用标准的膜片钳全细胞记录技术，我们研究了双氯芬酸钠、水杨酸和消炎痛对小鼠胸腺细胞通道电流和膜电容的影响。双氯芬酸钠和水杨酸显著抑制该通道的脉冲末端电流。然而，吲哚美辛抑制峰值和脉冲结束电流的膜电容显着增加。本研究首次证实了非甾体抗炎药，如双氯芬酸钠，水杨酸和吲哚美辛，对胸腺细胞Kv1.3通道电流产生抑制作用。吲哚美辛诱导的缓慢失活模式被认为与通过膜电容增加检测到的质膜表面的微观变化有关。
Lymphocytes predominantly express delayed rectifier K+-channels (Kv1.3) in their plasma membranes, and the channels play crucial roles in the lymphocyte activation and proliferation. Since nonsteroidal anti-inflammatory drugs (NSAIDs), the most commonly used analgesic and antipyretic drugs, exert immunomodulatory effects, they would affect the channel currents in lymphocytes. In the present study, employing the standard patch-clamp whole-cell recording technique, we examined the effects of diclofenac sodium, salicylate and indomethacin on the channel currents in murine thymocytes and the membrane capacitance. Diclofenac sodium and salicylate significantly suppressed the pulse-end currents of the channel. However, indomethacin suppressed both the peak and the pulse-end currents with a significant increase in the membrane capacitance. This study demonstrated for the first time that NSAIDs, such as diclofenac sodium, salicylate and indomethacin, exert inhibitory effects on thymocyte Kv1.3-channel currents. The slow inactivation pattern induced by indomethacin was thought to be associated with microscopic changes in the plasma membrane surface detected by the increase in the membrane capacitance.