Laboratorio de Fisiología Celular, Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile.
Millennium Nucleus for the Study of Pain (MiNuSPain), Santiago, Chile.
Cell Mol Neurobiol. 2023 Aug;43(6):2801-2813. doi: 10.1007/s10571-023-01318-8. Epub 2023 Jan 21.
Vagus nerve innervates several organs including the heart, stomach, and pancreas among others. Somas of sensory neurons that project through the vagal nerve are located in the nodose ganglion. The presence of purinergic receptors has been reported in neurons and satellite glial cells in several sensory ganglia. In the nodose ganglion, calcium depletion-induced increases in neuron activity can be partly reversed by P2X7 blockers applied directly into the ganglion. The later suggest a possible role of P2X7 receptors in the modulation of neuronal activity within this sensory ganglion. We aimed to characterize the response to P2X7 activation in nodose ganglion neurons under physiological conditions. Using an ex vivo preparation for electrophysiological recordings of the neural discharges of nodose ganglion neurons, we found that treatments with ATP induce transient neuronal activity increases. Also, we found a concentration-dependent increase in neural activity in response to Bz-ATP (ED = 0.62 mM, a selective P2X7 receptor agonist), with a clear desensitization pattern when applied every ~ 30 s. Electrophysiological recordings from isolated nodose ganglion neurons reveal no differences in the responses to Bz-ATP and ATP. Finally, we showed that the P2X7 receptor was expressed in the rat nodose ganglion, both in neurons and satellite glial cells. Additionally, a P2X7 receptor negative allosteric modulator decreased the duration of Bz-ATP-induced maximal responses without affecting their amplitude. Our results show the presence of functional P2X7 receptors under physiological conditions within the nodose ganglion of the rat, and suggest that ATP modulation of nodose ganglion activity may be in part mediated by the activation of P2X7 receptors.
迷走神经支配着包括心脏、胃和胰腺在内的多个器官。通过迷走神经投射的感觉神经元体位于结状神经节。已经在几个感觉神经节中的神经元和卫星神经胶质细胞中报道了嘌呤能受体的存在。在结状神经节中,通过直接向神经节中施加 P2X7 阻断剂,可以部分逆转钙耗竭诱导的神经元活动增加。这表明 P2X7 受体可能在调节该感觉神经节内的神经元活动中发挥作用。我们旨在在生理条件下表征 P2X7 激活对结状神经节神经元的反应。使用用于记录结状神经节神经元神经放电的离体制备物进行电生理记录,我们发现 ATP 处理会引起短暂的神经元活动增加。此外,我们发现神经活性对 Bz-ATP(ED = 0.62 mM,一种选择性 P2X7 受体激动剂)呈浓度依赖性增加,当每~30 秒应用一次时,表现出明显的脱敏模式。从分离的结状神经节神经元进行的电生理记录显示,Bz-ATP 和 ATP 的反应没有差异。最后,我们表明 P2X7 受体在大鼠结状神经节中表达,无论是在神经元还是卫星神经胶质细胞中。此外,P2X7 受体负变构调节剂降低了 Bz-ATP 诱导的最大反应的持续时间,而不影响其幅度。我们的结果表明,在大鼠结状神经节中,生理条件下存在功能性 P2X7 受体,并且提示 ATP 对结状神经节活性的调节可能部分是通过激活 P2X7 受体介导的。