Vanilloids selectively sensitize thermal glutamate release from TRPV1 expressing solitary tract afferents.
Vanilloids selectively sensitize thermal glutamate release from TRPV1 expressing solitary tract afferents.
复制标题
香草类选择性地敏化表达孤束传入神经的 TRPV1 的热谷氨酸释放。
DOI：
10.1016/j.neuropharm.2015.10.011
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发表时间：
2016
影响因子：
4.7
通讯作者：
Andresen,MichaelC
中科院分区：
文献类型：
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作者：
Hofmann,MackenzieE;Andresen,MichaelC
香草素、高温和低pH激活瞬时受体电位香草素1型（TRPV 1）受体。在脊髓背根神经节中，TRPV 1上这些门控位点之一的共激活通过其他模式敏化受体门控。在这里，在大鼠脑干切片中，我们研究了孤束核（NTS）神经元中的谷氨酸突触传递，其中大多数颅初级传入表达TRPV 1，但TRPV 1敏化是未知的。电刺激孤束（ST）诱发EPSC（ST-EPSC）。用辣椒素（100 nM）激活TRPV 1可增加自发性EPSC（sEPSC），但抑制ST-EPSC。高浓度的超强效香草素树脂毒素（RTX，1 nM）同样增加sEPSC率，但阻断ST-EPSC。将RTX浓度降低至150 pM适度增加了sEPSC的频率，而不会导致诱发的ST-EPSC失败。sEPSC速率随着浴温升高至36 °C而增加。这种热响应在150 pM RTX中更大，而ST-EPSC保持不受影响。香草素致敏的热反应持续在TTX，但被阻断的TRPV 1拮抗剂辣椒。我们的研究结果表明，TRPV 1的多模式激活促进sEPSC反应超过两种激活剂的算术和，即共激活使TRPV 1对自发谷氨酸释放的控制敏感。由于动作电位诱发的谷氨酸释放是不变的，这项工作提供了证据的协同性门控TRPV 1加上一个显着的分离的钙机制，管理独立的囊泡池负责自发和诱发释放在初级传入NTS。
Vanilloids, high temperature, and low pH activate the transient receptor potential vanilloid type 1 (TRPV1) receptor. In spinal dorsal root ganglia, co-activation of one of these gating sites on TRPV1 sensitized receptor gating by other modes. Here in rat brainstem slices, we examined glutamate synaptic transmission in nucleus of the solitary tract (NTS) neurons where most cranial primary afferents express TRPV1, but TRPV1 sensitization is unknown. Electrical shocks to the solitary tract (ST) evoked EPSCs (ST-EPSCs). Activation of TRPV1 with capsaicin (100 nM) increased spontaneous EPSCs (sEPSCs) but inhibited ST-EPSCs. High concentrations of the ultra-potent vanilloid resiniferatoxin (RTX, 1 nM) similarly increased sEPSC rates but blocked ST-EPSCs. Lowering the RTX concentration to 150 pM modestly increased the frequency of the sEPSCs without causing failures in the evoked ST-EPSCs. The sEPSC rate increased with raising bath temperature to 36 °C. Such thermal responses were larger in 150 pM RTX, while the ST-EPSCs remained unaffected. Vanilloid sensitization of thermal responses persisted in TTX but was blocked by the TRPV1 antagonist capsazepine. Our results demonstrate that multimodal activation of TRPV1 facilitates sEPSC responses in more than the arithmetic sum of the two activators, i.e. co-activation sensitizes TRPV1 control of spontaneous glutamate release. Since action potential evoked glutamate release is unaltered, the work provides evidence for cooperativity in gating TRPV1 plus a remarkable separation of calcium mechanisms governing the independent vesicle pools responsible for spontaneous and evoked release at primary afferents in the NTS.