The frequency of calcium oscillations induced by 5-HT, ACH, and KCl determine the contraction of smooth muscle cells of intrapulmonary bronchioles.
The frequency of calcium oscillations induced by 5-HT, ACH, and KCl determine the contraction of smooth muscle cells of intrapulmonary bronchioles.
复制标题
5-HT，ACH和KCL诱导的钙振荡的频率决定了肺内支气管的平滑肌细胞的收缩。
DOI：
10.1085/jgp.200409216
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发表时间：
2005-06
影响因子：
3.8
通讯作者：
Sanderson, Michael J
中科院分区：
文献类型：
--
作者：
Perez, Jose F;Sanderson, Michael J
肺内气道或血管阻力增加与哮喘或肺动脉高压有关，是平滑肌细胞收缩的结果。为了研究调节这些收缩的机制，我们开发了一种含有细支气管和小动脉的小鼠肺切片制剂，并使用相对比和共聚焦显微镜将收缩反应与SMCs [Ca2+]i的变化联系起来。气道是本研究的重点。激动剂5-羟色胺（5-HT）和乙酰胆碱（ACH）诱导气道的浓度依赖性收缩。高浓度KCl可引起气道SMCs的抽搐，但对气道大小影响不大。5-HT和ACH诱导[Ca2+]i的异步振荡，并在气道SMCs内以Ca2+波传播。Ca2+振荡的频率依赖于激动剂浓度，并与持续气道收缩的程度相关。在细胞外Ca2+缺乏或Ni2+存在的情况下，Ca2+振荡的频率下降，气道放松。相比之下，KCl诱导与SMC抽搐相关的低频Ca2+振荡。每一个kcl诱导的Ca2+振荡由一个大的Ca2+波组成，之前是多个局部Ca2+瞬态。kcl诱导的反应对神经递质阻滞剂有抗性，但被Ni2+或硝苯地平和缺乏细胞外Ca2+所消除。咖啡因消除了5-羟色胺、乙酰胆碱和KCl的收缩作用。这些结果表明(a) 5-HT和ACH通过启动Ca2+振荡诱导气道SMC收缩，(b) KCl通过超载和释放细胞内Ca2+诱导Ca2+瞬态和抽搐，(c)持续的，Ni2+敏感的Ca2+内流介导存储的再填充，以维持Ca2+振荡，反过来，SMC收缩，以及(d)气道SMC持续收缩的幅度受Ca2+振荡的频率调节。
Increased resistance of airways or blood vessels within the lung is associated with asthma or pulmonary hypertension and results from contraction of smooth muscle cells (SMCs). To study the mechanisms regulating these contractions, we developed a mouse lung slice preparation containing bronchioles and arterioles and used phase-contrast and confocal microscopy to correlate the contractile responses with changes in [Ca2+]i of the SMCs. The airways are the focus of this study. The agonists, 5-hydroxytrypamine (5-HT) and acetylcholine (ACH) induced a concentration-dependent contraction of the airways. High concentrations of KCl induced twitching of the airway SMCs but had little effect on airway size. 5-HT and ACH induced asynchronous oscillations in [Ca2+]i that propagated as Ca2+ waves within the airway SMCs. The frequency of the Ca2+ oscillations was dependent on the agonist concentration and correlated with the extent of sustained airway contraction. In the absence of extracellular Ca2+ or in the presence of Ni2+, the frequency of the Ca2+ oscillations declined and the airway relaxed. By contrast, KCl induced low frequency Ca2+ oscillations that were associated with SMC twitching. Each KCl-induced Ca2+ oscillation consisted of a large Ca2+ wave that was preceded by multiple localized Ca2+ transients. KCl-induced responses were resistant to neurotransmitter blockers but were abolished by Ni2+ or nifedipine and the absence of extracellular Ca2+. Caffeine abolished the contractile effects of 5-HT, ACH, and KCl. These results indicate that (a) 5-HT and ACH induce airway SMC contraction by initiating Ca2+ oscillations, (b) KCl induces Ca2+ transients and twitching by overloading and releasing Ca2+ from intracellular stores, (c) a sustained, Ni2+-sensitive, influx of Ca2+ mediates the refilling of stores to maintain Ca2+ oscillations and, in turn, SMC contraction, and (d) the magnitude of sustained airway SMC contraction is regulated by the frequency of Ca2+ oscillations.