钠泵同工酶在咳嗽受体中的选择性表达及其在咳嗽调节中的作用
2010/02/23
研究发现气道迷走传入神经一个新的亚型在调节咳嗽反射中具有重要作用。这些传入神经对点状机械刺激、酸和细胞外氯离子浓度下降极为敏感，但对辣椒素、缓激肽、组胺、腺苷、血清素或气道内压变化不敏感。本研究采用活体成像、逆行神经追踪及电生理分析，以明确该类神经对特殊机械刺激敏感性的结构基础，并进一步明确其兴奋性调节的特征。
结果显示，Na(+)-K(+) ATP酶的一种同工酶在咳嗽调节中具有极为重要的作用。上述迷走感觉神经元起源于双侧结状神经节，且可被苯乙烯染料FM2-10选择性染色。咳嗽受体末端嵌附于气道上皮细胞与平滑肌层之间的细胞外基质中，该处也是哮喘和慢性阻塞性肺疾病发生广泛气道重构的部位。咳嗽受体末端仅表达Na(+)-K(+)ATP酶的α3亚单位。经FM2-10体内活体染色显示，咳嗽受体在体外的兴奋性及体内的咳嗽反应可被钠泵抑制因子-哇巴因有效的选择性抑制。
上述结果首次对调节咳嗽的感觉神经元外周末梢的形态学结果进行了详细的描述，并明确了对其进行调节的一个选择性分子靶点。
（陈欣 审校）
J Neurosci. 2009 Oct 28;29(43):13662-13671.
Selective expression of a sodium pump isozyme by cough receptors and evidence for its essential role in regulating cough.
Mazzone SB, Reynolds SM, Mori N, Kollarik M, Farmer DG, Myers AC, Canning BJ.
We have identified a distinct subtype of airway vagal afferent nerve that plays an essential role in regulating the cough reflex. These afferents are exquisitely sensitive to punctate mechanical stimuli, acid, and decreases in extracellular chloride concentrations, but are insensitive to capsaicin, bradykinin, histamine, adenosine, serotonin, or changes in airway intraluminal pressures. In this study we used intravital imaging, retrograde neuronal tracing, and electrophysiological analyses to characterize the structural basis for their peculiar mechanical sensitivity and to further characterize the regulation of their excitability. In completing these experiments, we uncovered evidence for an essential role of an isozyme of Na(+)-K(+) ATPase in regulating cough. These vagal sensory neurons arise bilaterally from the nodose ganglia and are selectively and brilliantly stained intravitally with the styryl dye FM2-10. Cough receptor terminations are confined and adherent to the extracellular matrix separating the airway epithelium and smooth muscle layers, a site of extensive remodeling in asthma and chronic obstructive pulmonary disease. The cough receptor terminals uniquely express the alpha(3) subunit of Na(+)-K(+) ATPase. Intravital staining of cough receptors by FM2-10, cough receptor excitability in vitro, and coughing in vivo are potently and selectively inhibited by the sodium pump inhibitor ouabain. These data provide the first detailed morphological description of the peripheral terminals of the sensory nerves regulating cough and identify a selective molecular target for their modulation.
Mazzone SB, Reynolds SM, Mori N, et al. J Neurosci.2009Oct28;29(43):13662-71.
结果显示，Na(+)-K(+) ATP酶的一种同工酶在咳嗽调节中具有极为重要的作用。上述迷走感觉神经元起源于双侧结状神经节，且可被苯乙烯染料FM2-10选择性染色。咳嗽受体末端嵌附于气道上皮细胞与平滑肌层之间的细胞外基质中，该处也是哮喘和慢性阻塞性肺疾病发生广泛气道重构的部位。咳嗽受体末端仅表达Na(+)-K(+)ATP酶的α3亚单位。经FM2-10体内活体染色显示，咳嗽受体在体外的兴奋性及体内的咳嗽反应可被钠泵抑制因子-哇巴因有效的选择性抑制。
上述结果首次对调节咳嗽的感觉神经元外周末梢的形态学结果进行了详细的描述，并明确了对其进行调节的一个选择性分子靶点。
（陈欣 审校）
J Neurosci. 2009 Oct 28;29(43):13662-13671.
Selective expression of a sodium pump isozyme by cough receptors and evidence for its essential role in regulating cough.
Mazzone SB, Reynolds SM, Mori N, Kollarik M, Farmer DG, Myers AC, Canning BJ.
We have identified a distinct subtype of airway vagal afferent nerve that plays an essential role in regulating the cough reflex. These afferents are exquisitely sensitive to punctate mechanical stimuli, acid, and decreases in extracellular chloride concentrations, but are insensitive to capsaicin, bradykinin, histamine, adenosine, serotonin, or changes in airway intraluminal pressures. In this study we used intravital imaging, retrograde neuronal tracing, and electrophysiological analyses to characterize the structural basis for their peculiar mechanical sensitivity and to further characterize the regulation of their excitability. In completing these experiments, we uncovered evidence for an essential role of an isozyme of Na(+)-K(+) ATPase in regulating cough. These vagal sensory neurons arise bilaterally from the nodose ganglia and are selectively and brilliantly stained intravitally with the styryl dye FM2-10. Cough receptor terminations are confined and adherent to the extracellular matrix separating the airway epithelium and smooth muscle layers, a site of extensive remodeling in asthma and chronic obstructive pulmonary disease. The cough receptor terminals uniquely express the alpha(3) subunit of Na(+)-K(+) ATPase. Intravital staining of cough receptors by FM2-10, cough receptor excitability in vitro, and coughing in vivo are potently and selectively inhibited by the sodium pump inhibitor ouabain. These data provide the first detailed morphological description of the peripheral terminals of the sensory nerves regulating cough and identify a selective molecular target for their modulation.
Mazzone SB, Reynolds SM, Mori N, et al. J Neurosci.2009Oct28;29(43):13662-71.
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哮喘和慢性咳嗽患者的诱导痰液中的黏蛋白浓度
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高保真度咳嗽声响及气流特征记录系统
