Arachidonic acid potentiates acid-sensing ion channels in rat sensory neurons by a direct action
Arachidonic acid potentiates acid-sensing ion channels in rat sensory neurons by a direct action
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DOI：
10.1016/j.neuroscience.2006.12.024
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发表时间：
2007-03-16
期刊：
影响因子：
3.3
通讯作者：
McNaughton, P. A.
中科院分区：
文献类型：
--
作者：
Smith, E. S.;Cadiou, H.;McNaughton, P. A.
酸敏感离子通道（ASICs）被激活的细胞外pH值的降低。ASICs表达在伤害性感觉神经元，和几条线的证据表明，他们是负责信号的疼痛引起的细胞外酸化，但很少被理解的ASICs的调制促炎因子。使用全细胞膜片钳，我们证明，低pH值引起三个不同的内向电流在大鼠背根神经节神经元：缓慢失活的瞬态电流，快速失活的瞬态电流，和持续的电流。花生四烯酸（AA）可使这三种电流分别增强至峰值电流的123%、171%和264%。膜拉伸没有影响质子门控电流，这意味着AA是不可能通过局部膜变形。异源表达的ASIC1a和ASIC3携带的电流也被AA增强。AA通过直接机制增强ASIC激活，因为AA代谢的抑制对增强没有影响，并且在无细胞贴片中可以观察到单个ASIC 2a通道的增强。增强脂肪与AA相同的链长增加的双键的数量增加。已知AA在炎症中释放，结果表明AA可能是负责增强酸介导的疼痛的重要促炎剂。(c)2007年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Acid-sensing ion channels (ASICs) are activated by a decrease in extracellular pH. ASICs are expressed in nociceptive sensory neurons, and several lines of evidence suggest that they are responsible for signaling the pain caused by extracellular acidification, but little is understood of the modulation of ASICs by pro-inflammatory factors. Using whole-cell patch clamp we demonstrate that low pH evokes three distinct inward currents in rat dorsal root ganglion neurons: a slowly inactivating transient current, a rapidly inactivating transient current, and a sustained current. All three currents were potentiated by arachidonic acid (AA), to 123%, 171%, and 264% of peak current, respectively. Membrane stretch had no effect on proton-gated currents, implying that AA is unlikely to act via local membrane deformation. The current carried by heterologously expressed ASIC1a and ASIC3 was also potentiated by AA. AA potentiates ASIC activation by a direct mechanism, because inhibition of AA metabolism had no effect on potentiation, and potentiation of single ASIC2a channels could be observed in cell-free patches. Potentiation by lipids with the same chain length as AA increased as the number of double bonds was increased. AA is known to be released in inflammation and the results suggest that AA may be an important pro-inflammatory agent responsible for enhancing acid-mediated pain. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.