TRPM8 function and expression in vagal sensory neurons and afferent nerves innervating guinea pig esophagus.

TRPM8 function and expression in vagal sensory neurons and afferent nerves innervating guinea pig esophagus.
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TRPM8 在支配豚鼠食管的迷走感觉神经元和传入神经中的功能和表达。

DOI:
10.1152/ajpgi.00336.2014
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发表时间:
2015-03
期刊:
Am J Physiol Gastrointest Liver Physiol
影响因子:
--
通讯作者:
余晓云
余晓云
中科院分区:
其他
文献类型:
--
作者:
余晓云

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食管传入神经的感觉传导需要特定的离子通道和受体。TRPM 8是瞬时受体电位(TRP)通道家族的新成员,参与冷和薄荷脑诱导的感觉传导,但其在内脏感觉传导中的作用尚不清楚。本研究旨在确定TRPM 8在食管迷走神经传入亚型中的功能和表达。TRPM 8激动剂WS-12诱导的反应,首先确定在结和颈静脉神经元钙成像,然后研究了全细胞膜片钳记录在Dil标记的食管结和颈静脉神经元。在结状神经和颈静脉C纤维神经元中进行细胞外单单位记录,使用离体神经-迷走神经制剂,在食管中具有完整的神经末梢。用单神经元RT-PCR法检测Dil标记的食管结状核和颈静脉神经元TRPM 8 mRNA的表达。TRPM 8激动剂WS-12引起颈静脉神经元亚群中的钙内流,但不引起结状神经元中的钙内流。WS-12以剂量依赖性方式激活食管Dil标记的颈静脉神经元的外向整流电流,但不激活结状神经元的外向整流电流,这可以被TRPM 8抑制剂AMTB抑制。WS-12选择性地诱发食管颈静脉肌纤维动作电位放电,但不诱发结状C纤维。TRPM 8转录本在食管Dil标记的TRPV 1阳性颈静脉神经元中高度表达。总之,本研究证明了TRPM 8在食管迷走颈静脉中优先表达和功能,而不是结状神经元和C纤维亚型。这提供了一个独特的作用TRPM 8在食管感觉转导,并可能导致更好地了解食管感觉和伤害性感受的机制。
Sensory transduction in esophageal afferents requires specific ion channels and receptors. TRPM8 is a new member of the transient receptor potential (TRP) channel family and participates in cold- and menthol-induced sensory transduction, but its role in visceral sensory transduction is still less clear. This study aims to determine TRPM8 function and expression in esophageal vagal afferent subtypes. TRPM8 agonist WS-12-induced responses were first determined in nodose and jugular neurons by calcium imaging and then investigated by whole cell patch-clamp recordings in Dil-labeled esophageal nodose and jugular neurons. Extracellular single-unit recordings were performed in nodose and jugular C fiber neurons using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. TRPM8 mRNA expression was determined by single neuron RT-PCR in Dil-labeled esophageal nodose and jugular neurons. The TRPM8 agonist WS-12 elicited calcium influx in a subpopulation of jugular but not nodose neurons. WS-12 activated outwardly rectifying currents in esophageal Dil-labeled jugular but not nodose neurons in a dose-dependent manner, which could be inhibited by the TRPM8 inhibitor AMTB. WS-12 selectively evoked action potential discharges in esophageal jugular but not nodose C fibers. Consistently, TRPM8 transcripts were highly expressed in esophageal Dil-labeled TRPV1-positive jugular neurons. In summary, the present study demonstrated a preferential expression and function of TRPM8 in esophageal vagal jugular but not nodose neurons and C fiber subtypes. This provides a distinctive role of TRPM8 in esophageal sensory transduction and may lead to a better understanding of the mechanisms of esophageal sensation and nociception.
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