Activation of TREK currents by riluzole in three subgroups of cultured mouse nodose ganglion neurons.

Activation of TREK currents by riluzole in three subgroups of cultured mouse nodose ganglion neurons.
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riluzole在培养的小鼠节神经神经元的三个亚组中激活TREK电流。

DOI:
10.1371/journal.pone.0199282
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Lamas JA
Lamas JA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Fernández-Fernández D;Cadaveira-Mosquera A;Rueda-Ruzafa L;Herrera-Pérez S;Veale EL;Reboreda A;Mathie A;Lamas JA

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双孔结构域钾通道(K2P)是调控哺乳动物细胞背景钾电流的主要候选通道。TREK亚家族的通道由于对大量生理和物理刺激(pH、机械、温度)的敏感性,在感觉转导中也发挥着重要作用。根据我们之前关于迷走神经感觉系统中不同K2P通道的分子表达的报道,我们在这里证实了TREK通道在小鼠结节神经节(mNG)的神经元中具有功能性表达。根据神经元对河豚毒素和辣椒素的反应,将神经元分为A、Ah和C三组。将TREK亚家族激活剂利鲁唑应用于分离的mNG神经元,在所有三种亚型的大多数细胞中都产生了浓度依赖性的外向电流。利鲁唑作用于静息神经元时,膜电导增加,膜电位超极化约10毫伏。三组的静息电位相似,但C细胞的兴奋性明显较弱,在-100 mV时表现出较小的超极化激活电流,在-30 mV时表现出较小的持续电流。我们的研究结果表明,K2P通道的TREK亚家族可能在自主神经系统感觉神经元静息膜电位的维持中发挥重要作用,提示其参与迷走反射的调节。
Two-pore domain potassium channels (K2P) constitute major candidates for the regulation of background potassium currents in mammalian cells. Channels of the TREK subfamily are also well positioned to play an important role in sensory transduction due to their sensitivity to a large number of physiological and physical stimuli (pH, mechanical, temperature). Following our previous report describing the molecular expression of different K2P channels in the vagal sensory system, here we confirm that TREK channels are functionally expressed in neurons from the mouse nodose ganglion (mNG). Neurons were subdivided into three groups (A, Ah and C) based on their response to tetrodotoxin and capsaicin. Application of the TREK subfamily activator riluzole to isolated mNG neurons evoked a concentration-dependent outward current in the majority of cells from all the three subtypes studied. Riluzole increased membrane conductance and hyperpolarized the membrane potential by approximately 10 mV when applied to resting neurons. The resting potential was similar in all three groups, but C cells were clearly less excitable and showed smaller hyperpolarization-activated currents at -100 mV and smaller sustained currents at -30 mV. Our results indicate that the TREK subfamily of K2P channels might play an important role in the maintenance of the resting membrane potential in sensory neurons of the autonomic nervous system, suggesting its participation in the modulation of vagal reflexes.
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