Modulation of ASIC channels in rat cerebellar Purkinje neurons by ischaemia-related signals
Modulation of ASIC channels in rat cerebellar Purkinje neurons by ischaemia-related signals
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DOI：
10.1113/jphysiol.2002.020297
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发表时间：
2002-09-01
影响因子：
5.5
通讯作者：
Attwell, D
中科院分区：
文献类型：
--
作者：
Allen, NJ;Attwell, D
整个神经系统的神经元中都存在酸敏感离子通道 (ASIC)，可通过细胞外 pH 值的降低而激活。它们的氨基酸序列与膜拉伸激活的离子通道相似，并且与触觉有关。在这里，我们描述了小脑浦肯野细胞中 ASIC 的 pH 依赖性激活，并研究了它们如何受到缺血中释放的因子的调节。将外部 pH 从 7.4 降低会激活 -66 mV 的内向电流，主要由 Na+ 离子携带，在 pH 达到 6.4 时该电流是最大电流的一半，并被阿米洛利和钆阻断。 H+ 门控电流在几秒钟内变得不敏感，但大约 30% 的细胞响应 pH 6 溶液的持续存在而表现出持续的内向电流（峰值电流的 11%）。峰值 H+ 诱发电流通过膜拉伸（当 [K+](o) 升高时在缺血中发生）和花生四烯酸（当缺血中 [Ca2+](1) 升高时释放）增强。花生四烯酸使显示出由酸性 pH 引起的持续电流的细胞比例增加到 77%。乳酸（当新陈代谢在缺血中变成厌氧时释放）和 FMRFamide（可能模仿相关哺乳动物 RFamide 发射器的作用）也增强了 ASIC 电流。这些数据强化了 ASIC 通道功能的机械感觉方面的建议，并表明 ASIC 的激活反映了缺血期间存在的多种信号的整合。
Acid-sensing ion channels (ASICs), activated by a decrease of extracellular pH, are found in neurons throughout the nervous system. They have an amino acid sequence similar to that of ion channels activated by membrane stretch, and have been implicated in touch sensation. Here we characterize the pH-dependent activation of ASICs in cerebellar Purkinje cells and investigate how they are modulated by factors released in ischaemia. Lowering the external pH from 7.4 activated an inward current at -66 mV, carried largely by Na+ ions, which was half-maximal for a step to pH 6.4 and was blocked by amiloride and gadolinium. The H+-gated current desensitized within a few seconds, but approximately 30 % of cells showed a sustained inward current (11 % of the peak current) in response to the maintained presence of pH 6 solution. The peak H+-evoked current was potentiated by membrane stretch (which occurs in ischaemia when [K+](o) rises) and by arachidonic acid (which is released when [Ca2+](1) rises in ischaemia). Arachidonic acid increased to 77 % the fraction of cells showing a sustained current evoked by acid pH. The ASIC currents were also potentiated by lactate (which is released when metabolism becomes anaerobic in ischaemia) and by FMRFamide (which may mimic the action of related mammalian RFamide transmitters). These data reinforce suggestions of a mechanosensory aspect to ASIC channel function, and show that the activation of ASICs reflects the integration of multiple signals which are present during ischaemia.