Expression of transient receptor potential channels and two-pore potassium channels in subtypes of vagal afferent neurons in rat.

Expression of transient receptor potential channels and two-pore potassium channels in subtypes of vagal afferent neurons in rat.
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DOI:
10.1152/ajpgi.00396.2009
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发表时间:
2010-02
期刊:
American journal of physiology. Gastrointestinal and liver physiology
影响因子:
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通讯作者:
Huan Zhao;L. Sprunger;S. Simasko
Huan Zhao;L. Sprunger;S. Simasko
中科院分区:
其他
文献类型:
--
作者:
Huan Zhao;L. Sprunger;S. Simasko

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迷走神经传入神经元传递有关胃肠系统控制的重要信息。然而,由感觉输入引起的迷走神经激活的离子机制尚未完全理解。我们推测瞬时受体电位(TRP)通道和/或双孔钾(K2 p)通道是激活迷走神经传入的靶点。在这项研究中,我们探讨了这些通道的分布在迷走神经传入辣椒素治疗后,以消除辣椒素敏感的神经元,并通过单细胞PCR测量后,从胃或十二指肠逆行标记培养的迷走神经传入神经元的定量PCR。我们发现TRPC 1/3/5/6、TRPV 1 -4、TRPM 8、TRPA 1、TWIK 2、TRAAK、TREK 1和TASK 1/2都存在于大鼠结状神经节中。损伤结果和单细胞PCR结果表明,TRPA 1和TRPC 1优先表达在辣椒素敏感或TRPV 1阳性的神经元中。TRPM 8的表达在各种操作后动态变化,这可能解释了不同研究者获得的不同结果。最后,我们还检查了A型CCK受体(CCK-R(A))的离子通道分布,发现表达TRAAK的神经元明显偏好也表达CCK-R(A),特别是在肠神经支配的神经元中。这些发现,结合先前的研究结果,表明,背景电导,如TRPC 1,TRPA 1,和TRAAK确实差异分布在结状神经节,他们不仅与特定的标记物分离,但重叠的程度也取决于神经支配的目标。
Vagal afferent neurons relay important information regarding the control of the gastrointestinal system. However, the ionic mechanisms that underlie vagal activation induced by sensory inputs are not completely understood. We postulate that transient receptor potential (TRP) channels and/or two-pore potassium (K2p) channels are targets for activating vagal afferents. In this study we explored the distribution of these channels in vagal afferents by quantitative PCR after a capsaicin treatment to eliminate capsaicin-sensitive neurons, and by single-cell PCR measurements in vagal afferent neurons cultured after retrograde labeling from the stomach or duodenum. We found that TRPC1/3/5/6, TRPV1-4, TRPM8, TRPA1, TWIK2, TRAAK, TREK1, and TASK1/2 were all present in rat nodose ganglia. Both lesion results and single-cell PCR results suggested that TRPA1 and TRPC1 were preferentially expressed in neurons that were either capsaicin sensitive or TRPV1 positive. Expression of TRPM8 varied dynamically after various manipulations, which perhaps explains the disparate results obtained by different investigators. Last, we also examined ion channel distribution with the A-type CCK receptor (CCK-R(A)) and found there was a significant preference for neurons that express TRAAK to also express CCK-R(A), especially in gut-innervating neurons. These findings, combined with findings from prior studies, demonstrated that background conductances such as TRPC1, TRPA1, and TRAAK are indeed differentially distributed in the nodose ganglia, and not only do they segregate with specific markers, but the degree of overlap is also dependent on the innervation target.