Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo , Ribeirão Preto, São Paulo , Brazil.
J Neurophysiol. 2019 May 1;121(5):1822-1830. doi: 10.1152/jn.00279.2018. Epub 2019 Mar 20.
Sustained hypoxia (SH) activates chemoreceptors to produce cardiovascular and respiratory responses to bring the arterial partial pressure of O back to the physiological range. We evaluated the effect of SH (fraction of inspired O = 0.10, 24 h) on glutamatergic synaptic transmission and the interaction neuron-astrocyte in neurons of the nucleus tractus solitarii (NTS). Tractus solitarius (TS) fiber stimulation induced glutamatergic currents in neurons and astrocytes. SH increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate (AMPA/kainate) [-183 ± 122 pA ( = 10) vs. -353 ± 101 pA ( = 10)] and -methyl-d-aspartate (NMDA) current amplitude [61 ± 10 pA ( = 7) vs. 102 ± 37 pA ( = 10)]. To investigate the effects of SH, we used fluoroacetate (FAC), an astrocytic inhibitor, which revealed an excitatory modulation on AMPA/kainate current and an inhibitory modulation of NMDA current in control rats. SH blunted the astrocytic modulation of AMPA [artificial cerebrospinal fluid (aCSF): -353 ± 101 pA vs. aCSF + FAC: -369 ± 76 pA ( = 10)] and NMDA currents [aCSF: 102 ± 37 pA vs. aCSF + FAC: 108 ± 32 pA ( = 10)]. SH increased AMPA current density [control: -6 ± 3.5 pA/pF ( = 6) vs. SH: -20 ± 12 pA/pF ( = 7)], suggesting changes in density, conductance, or affinity of AMPA receptors. SH produced no effect on astrocytic resting membrane potential, input resistance, and AMPA/kainate current. We conclude that SH decreased the neuron-astrocyte interaction at the NTS level, facilitating the glutamatergic transmission, which may contribute to the enhancement of cardiovascular and respiratory responses to baro- and chemoreflexes activation in SH rats. Using an electrophysiological approach, we have shown that in nucleus tractus solitarii (NTS) from control rats, astrocytes modulate the AMPA and NMDA currents in NTS neurons, changing their excitability. Sustained hypoxia (SH) increased both glutamatergic currents in NTS neurons due to ) a reduction in the astrocytic modulation and ) an increase in the density of AMPA receptors. These new findings show the importance of neuron-astrocyte modulation in the excitatory synaptic transmission in NTS of control and SH rats.
持续缺氧 (SH) 激活化学感受器，产生心血管和呼吸反应，使动脉血氧分压恢复到生理范围。我们评估了 SH（吸入氧分数 = 0.10，24 小时）对孤束核（NTS）神经元中谷氨酸能突触传递和神经元-星形胶质细胞相互作用的影响。孤束束纤维刺激诱导神经元和星形胶质细胞中的谷氨酸能电流。SH 增加 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸/ kainate (AMPA/kainate) [(-183±122 pA (=10) 与 (-353±101 pA (=10)] 和 - 甲基-d-天冬氨酸 (NMDA) 电流幅度[61±10 pA (=7) 与 102±37 pA (=10)]。为了研究 SH 的影响，我们使用氟乙酸盐 (FAC)，一种星形胶质细胞抑制剂，发现其对 AMPA/kainate 电流有兴奋调节作用，对 NMDA 电流有抑制调节作用。SH 减弱了 AMPA 的星形胶质细胞调节[人工脑脊液 (aCSF)：-353±101 pA 与 aCSF+FAC：-369±76 pA (=10)] 和 NMDA 电流[aCSF：102±37 pA 与 aCSF+FAC：108±32 pA (=10)]。SH 增加了 AMPA 电流密度[对照：-6±3.5 pA/pF (=6) 与 SH：-20±12 pA/pF (=7)]，提示 AMPA 受体的密度、电导或亲和力发生了变化。SH 对星形胶质细胞静息膜电位、输入电阻和 AMPA/kainate 电流没有影响。我们得出结论，SH 降低了 NTS 水平神经元-星形胶质细胞相互作用，促进了谷氨酸能传递，这可能有助于增强 SH 大鼠压力和化学反射激活时的心血管和呼吸反应。我们使用电生理学方法表明，在对照大鼠的孤束核 (NTS) 中，星形胶质细胞调节 NTS 神经元中的 AMPA 和 NMDA 电流，改变其兴奋性。持续缺氧 (SH) 增加了 NTS 神经元中的谷氨酸能电流，这是由于)星形胶质细胞调节的减少和) AMPA 受体密度的增加。这些新发现表明，在对照和 SH 大鼠的 NTS 中，神经元-星形胶质细胞调节在兴奋性突触传递中非常重要。
