The modulation of voltage-gated potassium channels by anisotonicity in trigeminal ganglion neurons
The modulation of voltage-gated potassium channels by anisotonicity in trigeminal ganglion neurons
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DOI：
10.1016/j.neuroscience.2008.03.046
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发表时间：
2008-06-23
期刊：
影响因子：
3.3
通讯作者：
Liu, L.
中科院分区：
文献类型：
--
作者：
Chen, L.;Liu, C.;Liu, L.
电压门控钾通道（VGPCs）通过控制细胞的电特性和兴奋性，在许多生理功能中起着重要作用。周围神经系统紧张性的变化可以激活伤害感受器并产生疼痛。在这里，我们使用全细胞膜片钳技术，探讨了低张力和高张力如何调节培养的大鼠和小鼠三叉神经节（TG）神经元的VGPCs。我们发现，低张力和高张力对慢速失活的K+电流（I-K）和快速失活的K+电流（I-A）有不同的影响：低张力增加了I-K，但对I-A没有影响，而高张力同时降低了I-K和I-A。瞬时受体电位vanilloid 4（TRPV4）受体激活剂4 α - phorpol -12,13-didecanoate （4 α - pdd）可以模拟低张力引起的I-K升高，但TRPV4（-/-）小鼠TG神经元的低张力并未增加，提示TRPV4受体参与了低张力诱导的反应。我们还发现PKC的失活选择性地逆转了低渗性对I-K的增加，而g蛋白的拮抗选择性地恢复了高渗性对I-K和I-A的抑制，这表明低渗性和高渗性的调节需要不同的细胞内信号通路。总之，渗透压的变化对I-K和I-A有不同的影响，不同的受体和第二信使系统对低张力和高张力诱导的VGPCs的调节有选择性。(c) 2008 ibro。Elsevier Ltd.出版。版权所有。
Voltage-gated potassium channels (VGPCs) play an important role in many physiological functions by controlling the electrical properties and excitability of cells. Changes in tonicity in the peripheral nervous system can activate nociceptors and produce pain. Here, using whole cell patch clamp techniques, we explore how hypo- and hypertonicity modulate VGPCs in cultured rat and mouse trigeminal ganglion (TG) neurons. We found that hypo- and hypertonicity had different effects on slow-inactivating K+ current (I-K) and fast-inactivating K+ current (I-A): hypotonicity increased I-K but had no effect on I-A while hypertonicity depressed both I-K and I-A. The increase of I-K by hypotonicity was mimicked by transient receptor potential vanilloid 4 (TRPV4) receptor activator 4 alpha-phorbol-12,13-didecanoate (4 alpha-PDD) but hypotonicity did not exhibit increase in TRPV4(-/-) mice TG neurons, suggesting that TRPV4 receptor was involved in hypotonicity-induced response. We also found that inactivation of PKC selectively reversed the increase of I-K by hypotonicity, whereas antagonism of G-protein selectively rescued the inhibitions of I-K and I-A by hypertonicity, indicating that different intracellular signaling pathways were required for the modulation by hypo- and hypertonicity. In summary, changes in osmolality have various effects on I-K and I-A and different receptors and second messenger systems are selective for the modulation of VGPCs induced by hypo- versus hypertonicity. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.