Acid sensing ion channel 1 in lateral hypothalamus contributes to breathing control.
Acid sensing ion channel 1 in lateral hypothalamus contributes to breathing control.
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下丘脑外侧酸感应离子通道 1 有助于呼吸控制
DOI：
10.1371/journal.pone.0039982
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Shen L
中科院分区：
文献类型：
--
作者：
Song N;Zhang G;Geng W;Liu Z;Jin W;Li L;Cao Y;Zhu D;Yu J;Shen L
酸敏感离子通道（asic）存在于神经元中，可能有助于化学接受。在asic的6个亚基中，ASIC1主要表达于中枢神经系统。最近，包括外侧下丘脑（LH）在内的大脑多个部位被发现对细胞外酸化敏感。由于LH含有食欲素神经元并支配髓质呼吸中枢，我们假设ASIC1在食欲素神经元上表达，并参与酸诱导的呼吸驱动的增加。为了验证这一假设，我们使用双免疫荧光检测ASIC1是否在LH的食欲素神经元上表达，并评估完整大鼠对LH酸化的反应。我们发现ASIC1在LH中与orexinA共定位。微注射酸化人工脑脊液可使iPND振幅增加70% (pH 7.4 vs . pH 6.5∶1.05±0.12 vs . 1.70±0.10,n = 6， P<0.001)，使呼吸驱动（iPND峰值振幅/吸气时间，PA/Ti）增加40%（1.10±0.23 vs . 1.50±0.38，P<0.05）。这种刺激作用可以通过非选择性抑制剂（amiloride 10 mM）、选择性抑制剂（PcTX1, 10 nM）阻断ASIC1或通过破坏LH中的食欲素神经元来消除。目前的研究结果支持了我们的假设，即在局部酸中毒时，LH中的食欲素神经元可以通过ASIC1对呼吸发挥兴奋作用。由于中枢酸化与多种肺部疾病的呼吸功能障碍有关，了解其潜在机制可以改善患者管理。
Acid-sensing ion channels (ASICs) are present in neurons and may contribute to chemoreception. Among six subunits of ASICs, ASIC1 is mainly expressed in the central nervous system. Recently, multiple sites in the brain including the lateral hypothalamus (LH) have been found to be sensitive to extracellular acidification. Since LH contains orexin neurons and innervates the medulla respiratory center, we hypothesize that ASIC1 is expressed on the orexin neuron and contributes to acid-induced increase in respiratory drive. To test this hypothesis, we used double immunofluorescence to determine whether ASIC1 is expressed on orexin neurons in the LH, and assessed integrated phrenic nerve discharge (iPND) in intact rats in response to acidification of the LH. We found that ASIC1 was co-localized with orexinA in the LH. Microinjection of acidified artificial cerebrospinal fluid increased the amplitude of iPND by 70% (pH 7.4 v.s. pH 6.5∶1.05±0.12 v.s. 1.70±0.10, n = 6, P<0.001) and increased the respiratory drive (peak amplitude of iPND/inspiratory time, PA/Ti) by 40% (1.10±0.23 v.s. 1.50±0.38, P<0.05). This stimulatory effect was abolished by blocking ASIC1 with a nonselective inhibitor (amiloride 10 mM), a selective inhibitor (PcTX1, 10 nM) or by damaging orexin neurons in the LH. Current results support our hypothesis that the orexin neuron in the LH can exert an excitation on respiration via ASIC1 during local acidosis. Since central acidification is involved in breathing dysfunction in a variety of pulmonary diseases, understanding its underlying mechanism may improve patient management.
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影响因子：
2.3
作者：
Dias, Mirela Barros;Li, Aihua;Nattie, Eugene
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Nattie, Eugene
影响因子：
5.3
作者：
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发表时间：
2011-01
期刊：
Acta physiologica (Oxford, England)
影响因子：
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作者：
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通讯作者：
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影响因子：
5.5
作者：
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