Relationship between asynchronous Ca2+ waves and force development in intact smooth muscle bundles of the porcine trachea

Relationship between asynchronous Ca2+ waves and force development in intact smooth muscle bundles of the porcine trachea
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DOI:
10.1152/ajplung.00043.2003
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发表时间:
2003-12-01
影响因子:
4.9
通讯作者:
van Breemen, C
van Breemen, C
中科院分区:
医学2区
文献类型:
--
作者:
Kuo, KH;Dai, JZ;van Breemen, C

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细胞内钙离子浓度([Ca 2 +](i))的波动是气道平滑肌细胞(ASMC)兴奋-收缩偶联(E-C偶联)的主要环节。最近有报道,ACh诱导小鼠细支气管ASMC的异步重复钙波。通过使用一种新的技术,使我们能够同时测量位于完整气管肌束内的ASMC中的亚细胞[Ca 2 +](i)和力的产生,我们研究了气管中类似的Ca 2+信号模式。我们发现,ACh的应用导致产生的循环胞内Ca 2+波进展沿着的带状完整的ASMC的纵轴。这些Ca 2+波在相邻细胞之间不同步,并且波形[Ca 2 +](i)振荡的诱导与气管肌束的力的发展在时间上相关。通过比较力产生的浓度依赖性和表征[Ca 2 +](i)振荡的参数,我们发现,ACh诱导的气管平滑肌束的力发展的浓度依赖性增加是通过完整ASMC的差异募集来启动Ca 2+波和[Ca 2 +](i)振荡频率的增强和峰间[Ca 2 +](i)升高来实现的。一旦细胞被招募。我们的研究结果表明,异步重复的Ca ~(2+)波的基础ACh诱导的收缩完整的气管平滑肌束的E-C耦合。此外,与在酶促解离的ASMC中报道的相反,通过L型电压门控Ca 2+通道的Ca 2+内流不是ACh刺激的完整ASMC中产生[Ca 2 +](i)振荡和力发展的强制性要求。
Fluctuations in intracellular calcium concentration ([Ca2+](i)) constitute the main link in excitation-contraction coupling (E-C coupling) in airway smooth muscle cells (ASMC). It has recently been reported that ACh induces asynchronous recurring Ca2+ waves in intact ASMC of murine bronchioles. With the use of a novel technique allowing us to simultaneously measure subcellular [Ca2+](i) and force generation in ASMC located within an intact tracheal muscle bundle, we examined a similar pattern of Ca2+ signaling in the trachea. We found that application of ACh resulted in the generation of recurring intracellular Ca2+ waves progressing along the longitudinal axis of the ribbon-shaped intact ASMC. These Ca2+ waves were not synchronized between neighboring cells, and induction of wave-like [Ca2+](i) oscillations was temporally associated with development of force by the tracheal muscle bundle. By comparing the concentration dependence of force generation and the parameters characterizing the [Ca2+](i) oscillations, we found that the concentration-dependent increase in ACh-induced force development by the tracheal smooth muscle bundle is achieved by differential recruitment of intact ASMC to initiate Ca2+ waves and by enhancement in the frequency of [Ca2+](i) oscillations and elevation of interspike [Ca2+](i) once the cells are recruited. Our findings demonstrate that asynchronous recurring Ca2+ waves underlie E-C coupling in ACh-induced contraction of the intact tracheal smooth muscle bundle. Furthermore, in contrast to what was reported in enzymatically dissociated ASMC, Ca2+ influx through the L-type voltage-gated Ca2+ channel was not an obligatory requirement for the generation of [Ca2+](i) oscillations and development of force in ACh-stimulated intact ASMC.