Chemosensitive Phox2b-expressing neurons are crucial for hypercapnic ventilatory response in the nucleus tractus solitarius
Chemosensitive Phox2b-expressing neurons are crucial for hypercapnic ventilatory response in the nucleus tractus solitarius
复制标题
表达化学敏感性 Phox2b 的神经元对于孤束核高碳酸血症通气反应至关重要
DOI：
10.1113/jp274437
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发表时间：
2017-07-15
影响因子：
5.5
通讯作者：
Wang, Sheng
中科院分区：
文献类型：
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作者：
Fu, Congrui;Xue, Jinyu;Wang, Sheng
孤束核（NTS）神经元被认为具有中枢呼吸化学感受器的功能。然而，为这些神经元定义的共同分子标记物仍然未知。本研究探讨了是否配对样同源框2b（Phox2b）表达NTS神经元招募高碳酸血症的缓解反应（HCVR），以及这些神经元是否表现出内在的化学敏感性。使用全身体积描记法评估HCVR，并通过膜片钳记录在来自Phox2b-EGFP转基因小鼠的脑干切片或分离的神经元中检查神经元化学敏感性。将神经毒素物质P-saporin（SSP-SAP）注射到NTS中破坏了Phox2b表达神经元。分钟通气量和潮气量都减少了13%，在暴露于8%CO2吸入空气时，类似于13%的Phox2b表达神经元被淘汰。然而，当受到>= 4%CO2的挑战时，这些神经元的损失接近18%，与分钟通气量显著减少>= 18%和潮气量显著减少>= 22%相关。在这两种情况下，呼吸频率不受影响。大多数CO2激活的神经元对Phox2b呈免疫反应性。在脑干切片中，来自Phox2b-EGFP小鼠的类似于43%的Phox2b表达神经元在生理酸化（pH7.0或8%CO2）期间显示出持续或短暂的放电率增加。这种反应也存在于有利于内在属性的解离神经元中。在电压钳记录中，在Phox2b表达神经元的一个亚组中发现了背景K+通道样电流。因此，呼吸赤字所造成的注射SSP-SAP到NTS是由于成比例的病变CO2/H+敏感的Phox2b表达神经元。
The nucleus tractus solitarius (NTS) neurons have been considered to function as central respiratory chemoreceptors. However, the common molecular marker defined for these neurons remains unknown. The present study investigated whether paired-like homeobox 2b (Phox2b)-expressing NTS neurons are recruited in hypercapnic ventilatory response (HCVR) and whether these neurons exhibit intrinsic chemosensitivity. HCVR was assessed using whole body plethysmography and neuronal chemosensitivity was examined by patch clamp recordings in brainstem slices or dissociated neurons from Phox2b-EGFP transgenic mice. Injection of the neurotoxin substance P-saporin (SSP-SAP) into NTS destroyed Phox2b-expressing neurons. Minute ventilation and tidal volume were both reduced by 13% during exposure to 8% CO2 in inspired air when similar to 13% of the Phox2b-expressing neurons were eliminated. However, a loss of similar to 18% of these neurons was associated with considerable decreases in minute ventilation by >= 18% and in tidal volume by >= 22% when challenged by >= 4% CO2. In both cases, breathing frequency was unaffected. Most CO2-activated neurons were immunoreactive to Phox2b. In brainstem slices, similar to 43% of Phox2b-expressing neurons from Phox2b-EGFP mice displayed a sustained or transient increase in firing rate during physiological acidification (pH7.0 or 8% CO2). Such a response was also present in dissociated neurons in favour of an intrinsic property. In voltage clamp recordings, a background K+ channel-like current was found in a subgroup of Phox2b-expressing neurons. Thus, the respiratory deficits caused by injection of SSP-SAP into the NTS are attributable to proportional lesions of CO2/H+-sensitive Phox2b-expressing neurons.