Activation of TRPA1 channel facilitates excitatory synaptic transmission in substantia gelatinosa neurons of the adult rat spinal cord
Activation of TRPA1 channel facilitates excitatory synaptic transmission in substantia gelatinosa neurons of the adult rat spinal cord
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DOI：
10.1523/jneurosci.0557-07.2007
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发表时间：
2007-04-18
影响因子：
5.3
通讯作者：
Kumamoto, Eiichi
中科院分区：
文献类型：
--
作者：
Kosugi, Masafumi;Nakatsuka, Terumasa;Kumamoto, Eiichi
TRPA1在初级感觉神经元和毛细胞中表达，被认为可以被冷刺激、机械刺激或刺激性成分激活。然而，它在调节突触传递中的作用还没有文献记载。本研究采用全细胞膜片钳技术，观察了激活TRPA1通道对成年大鼠脊髓切片胶状质(SG)神经元突触传递的影响。芥子油的主要成分异硫氰酸烯丙酯(AITC)灌流2min可显著增加自发EPSCs(SEPSCs)的频率和幅度，并伴有内向电流。肉桂醛和大蒜素也有类似的作用。AITC诱导的sEPSC频率和幅度的增加对河豚毒素(TTX)和La3+有抵抗作用，而在无ACA(2+)的镀液中则显著降低。在谷氨酸受体拮抗剂CNQX和AP5存在下，AITC不产生任何突触活动。Ru红可降低AITC引起的sEPSC频率和幅度的增加，而卡萨西平对其无影响。AITC还增加自发抑制性突触后电流的频率和幅度；这种作用在TTX或谷氨酸受体拮抗剂存在时被取消。这些结果表明，TRPA1不仅定位于SG神经元的突触前终末以促进谷氨酸的释放，而且也定位于支配脊髓抑制性中间神经元的初级传入终末，与SG神经元形成突触。这种感觉信号的中枢调节可能与生理和病理性痛感有关。
TRPA1 is expressed in primary sensory neurons and hair cells, and it is proposed to be activated by cold stimuli, mechanical stimuli, or pungent ingredients. However, its role in regulating synaptic transmission has never been documented yet. In the present study, we examined whether activation of the TRPA1 channels affects synaptic transmission in substantia gelatinosa (SG) neurons of adult rat spinal cord slices by using the whole-cell patch-clamp technique. A chief ingredient of mustard oil, allyl isothiocyanate ( AITC), superfused for 2 min markedly increased the frequency and amplitude of spontaneous EPSCs (sEPSCs), which was accompanied by an inward current. Similar actions were produced by cinnamaldehyde and allicin. The AITC-induced increases in sEPSC frequency and amplitude were resistant to tetrodotoxin (TTX) and La3+, whereas being significantly reduced in extent in aCa(2+)-free bath solution. In the presence of glutamate receptor antagonists CNQX and AP5, AITC did not generate any synaptic activities. The AITC-induced increases in sEPSC frequency and amplitude were reduced by ruthenium red, whereas being unaffected by capsazepine. AITC also increased the frequency and amplitude of spontaneous inhibitory postsynaptic currents; this AITC action was abolished in the presence of TTX or glutamate receptor antagonists. These results indicate that TRPA1 appears to be localized not only at presynaptic terminals on SG neurons to enhance glutamate release, but also in terminals of primary afferents innervating onto spinal inhibitory interneurons, which make synapses with SG neurons. This central modulation of sensory signals may be associated with physiological and pathological pain sensations.