Kosugi Masafumi, Nakatsuka Terumasa, Fujita Tsugumi, Kuroda Yasuo, Kumamoto Eiichi
Department of Physiology, Faculty of Medicine, Saga University, Saga 849-8501, Japan.
J Neurosci. 2007 Apr 18;27(16):4443-51. doi: 10.1523/JNEUROSCI.0557-07.2007.
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 a Ca2+-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.
瞬时受体电位锚蛋白1（TRPA1）在初级感觉神经元和毛细胞中表达，据推测它可被冷刺激、机械刺激或刺激性成分激活。然而，其在调节突触传递中的作用尚未见报道。在本研究中，我们使用全细胞膜片钳技术研究了TRPA1通道的激活是否会影响成年大鼠脊髓切片胶状质（SG）神经元中的突触传递。芥末油的主要成分异硫氰酸烯丙酯（AITC）灌流2分钟可显著增加自发性兴奋性突触后电流（sEPSCs）的频率和幅度，并伴有内向电流。肉桂醛和大蒜素也产生了类似的作用。AITC诱导的sEPSC频率和幅度增加对河豚毒素（TTX）和La3 +具有抗性，而在无Ca2 +的浴液中其程度显著降低。在存在谷氨酸受体拮抗剂CNQX和AP5的情况下，AITC不会产生任何突触活动。AITC诱导的sEPSC频率和幅度增加被钌红降低，而不受辣椒素的影响。AITC还增加了自发性抑制性突触后电流的频率和幅度；在存在TTX或谷氨酸受体拮抗剂的情况下，这种AITC作用被消除。这些结果表明，TRPA1似乎不仅定位于SG神经元的突触前终末以增强谷氨酸释放，还定位于支配脊髓抑制性中间神经元并与SG神经元形成突触的初级传入神经终末。这种对感觉信号的中枢调节可能与生理和病理性痛觉有关。
