Enhancement of airway ciliary beating mediated via voltage-gated Ca2+ channels/α7-nicotinic receptors in mice
Enhancement of airway ciliary beating mediated via voltage-gated Ca2+ channels/α7-nicotinic receptors in mice
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通过电压门控 Ca2+ 通道/α7-烟碱受体介导的小鼠气道纤毛跳动的增强
DOI：
10.1007/s00424-022-02724-5
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Nakahari Takashi
中科院分区：
文献类型：
--
作者：
Saitoh Daichi;Kawaguchi Kotoku;Asano Shinji;Inui Toshio;Marunaka Yoshinori;Nakahari Takashi
乙酰胆碱(ACh)激活M受体(MAChRs)和烟碱型ACh受体(NAChRs)，通过增加细胞内钙离子浓度([Ca~(2+)]i)来增强纤毛搏动。NAChRs增强呼吸道纤毛搏动的机制目前仍不清楚，尽管mAChRs的作用机制已为人所熟知。在本研究中，我们重点研究了α7-nAChRs和电压门控钙通道(CAVs)在气道纤毛搏动中的作用。用高速视频显微镜测量纤毛搏动的频率(CBF)和振幅(CBD)来评价纤毛搏动的活动。ACh通过mAChRs和α7-nAChRs(nAChR的一个亚单位)刺激的[Ca~(2+)]i升高，使小鼠气道纤毛细胞的血流量和血流量增加25%。用α7-nAChR的激动剂PNU282987和α7-nAChR的抑制剂MLA进行的实验表明，α7-nAChR增强的脑血流量和脑血流速度约为ACh的50%。硝苯地平可抑制α7-nAChRs对CBF、CBD和[Ca~(2+)]i的增强作用，提示α7-nAChRs对CAV有激活作用。使用含或不含硝苯地平(155.5 mM K+)的高K+溶液的实验表明，CAV的激活通过增加[Ca~(2+)]i来增加脑血流量和脑血流量。免疫荧光和免疫印迹研究表明，Cav1.2和α7-nAChR在呼吸道纤毛中有表达。此外，IL-13刺激纤毛细胞MLA敏感的CBF和CBD增加，提示CaV1.2/α7-nAChR/ACh对纤毛搏动具有自分泌调节作用。总之，CaV1.2/α7-nAChR是呼吸道纤毛中一种新的钙信号转导途径，它能增强CBF和CBD，并激活粘液纤毛清除，维持健康的呼吸道。
Acetylcholine (ACh), which activates muscarinic ACh receptors (mAChRs) and nicotinic ACh receptors (nAChRs), enhances airway ciliary beating by increasing the intracellular Ca2+concentration ([Ca2+]i). The mechanisms enhancing airway ciliary beating by nAChRs have remained largely unknown, although those by mAChRs are well understood. In this study, we focused on the effects of α7-nAChRs and voltage-gated Ca2+channels (CaVs) on the airway ciliary beating. The activities of ciliary beating were assessed by frequency (CBF, ciliary beat frequency) and amplitude (CBD, ciliary bend distance) measured by high-speed video microscopy. ACh enhanced CBF and CBD by 25% mediated by an [Ca2+]iincrease stimulated by mAChRs and α7-nAChRs (a subunit of nAChR) in airway ciliary cells of mice. Experiments using PNU282987 (an agonist of α7-nAChR) and MLA (an inhibitor of α7-nAChR) revealed that CBF and CBD enhanced by α7-nAChR are approximately 50% of those enhanced by ACh. CBF, CBD, and [Ca2+]ienhanced by α7-nAChRs were inhibited by nifedipine, suggesting activation of CaVs by α7-nAChRs. Experiments using a high K+solution with/without nifedipine (155.5 mM K+) showed that the activation of CaVs enhances CBF and CBD via an [Ca2+]iincrease. Immunofluorescence and immunoblotting studies demonstrated that Cav1.2 and α7-nAChR are expressed in airway cilia. Moreover, IL-13 stimulated MLA-sensitive increases in CBF and CBD in airway ciliary cells, suggesting an autocrine regulation of ciliary beating by CaV1.2/α7-nAChR/ACh. In conclusion, a novel Ca2+signalling pathway in airway cilia, CaV1.2/α7-nAChR, enhances CBF and CBD and activates mucociliary clearance maintaining healthy airways.
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DOI：
10.1085/jgp.201812126
发表时间：
2018-12-03
期刊：
The Journal of general physiology
影响因子：
--
作者：
Takeuchi H;Kurahashi T
通讯作者：
Kurahashi T
影响因子：
5.8
作者：
Papke RL
通讯作者：
Papke RL
Takashi Hirano：“CD9 参与人类滋养细胞样绒毛膜癌细胞系 BeWo 细胞的侵袭”《分子人类生殖》。
DOI：
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发表时间：
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DOI：
10.1165/rcmb.2011-0171oc
发表时间：
2012-01-01
影响因子：
6.4
作者：
Hollenhorst, Monika I.;Lips, Katrin S.;Fronius, Martin
通讯作者：
Fronius, Martin
哺乳动物烟碱乙酰胆碱受体：从结构到功能。
影响因子：
33.6
作者：
Albuquerque EX;Pereira EF;Alkondon M;Rogers SW
通讯作者：
Rogers SW