Modulation of Muscle rNav 1.4 Na+ Channel Isoform by Arachidonic Acid and Its Non-Metabolized Analog
Modulation of Muscle rNav 1.4 Na+ Channel Isoform by Arachidonic Acid and Its Non-Metabolized Analog
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DOI：
10.1002/jcp.21664
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发表时间：
2009-04-01
影响因子：
5.6
通讯作者：
Mei, Yan-Ai
中科院分区：
文献类型：
--
作者：
Gu, Hua;Fang, Yan-Jia;Mei, Yan-Ai
花生四烯酸(AA)及其代谢产物是重要的第二信使，发挥着多种生物学作用，包括调节各种离子通道。然而，AA对肌肉Na+通道异构体的阻断作用尚未被详细研究。在这里，我们研究了AA对肌肉RNA(V)1.4亚型在人胚胎肾293细胞中表达的调节作用。结果表明，AA对RNA(V)1.4电流既有激活作用，又有抑制作用，这取决于去极化电位的大小：AA使去极化-30 mV或-40 mV诱发的RNA(V)1.4电流增加，而使膜电位大于-10 mV诱发的RNA(V)1.4电流显著降低。在1-500 mU M浓度范围内，AA对RNA(V)1.4电流的抑制作用呈剂量依赖性和可逆性。除了调节RNA(V)1.4电流的幅度外，AA还显著调节了RNA(V)1.4通道的稳态激活和失活特性。此外，AA处理导致RNA(V)1.4通道从失活状态恢复得相当缓慢；然而，AA的抑制作用不会因重复脉冲或改变频率而改变。AA对RNA(V)1.4电流的作用完全被AA的非代谢类似物ETYA所模拟。我们的数据表明，AA，而不是AA的代谢产物，可以电压依赖地调制RNA(V)1.4电流。
Arachidonic acid (AA) and its metabolic products are important second messengers which exert many biological actions, including modulation of various ion channels. However, the blockage of muscle Na+ channel isoforms by AA has not been examined in detail. Here, we investigated the modulating effects of AA on muscle rNa(v) 1.4 isoforms expressed in human embryonic kidney 293 cells. The results revealed that AA has both activation and inhibitory effects on rNa(v) 1.4 currents depending on the depolarizing potential: AA increased the rNa(v) 1.4 current evoked by a depolarization of -30 or -40 mV, but significantly decreased the rNa(v) 1.4 current evoked by a depolarization of membrane potential over -10 mV. At concentrations of 1-500 mu M, the inhibitory effect on the rNa(v) 1.4 current induced by AA was dose-dependent and reversible. In addition to modulating the amplitude of the rNa(v) 1.4 current, AA significantly modulated the steady-state activation and inactivation properties of rNa(v) 1.4 channels. Furthermore, treatment with AA resulted in a fairly slow recovery of the rNa(v) 1.4 channel from inactivation; however, the inhibitory effect of AA was not changed by repetitive pulses or by changing frequency. The effect of AA on rNa(v) 1.4 currents was completely mimicked by ETYA, the non-metabolized analog of AA. Our data demonstrated that AA, but not the metabolic products of AA, can voltage-dependent modulate rNa(v) 1.4 currents.