Nitric oxide mediates stretch-induced Ca2+ oscillation in smooth muscle
Nitric oxide mediates stretch-induced Ca2+ oscillation in smooth muscle
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DOI：
10.1242/jcs.180638
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发表时间：
2016-06
影响因子：
4
通讯作者：
Ji Zheng;Kui Zhai;Yingxiao Chen;Xu Zhang;Lin Miao;Bin Wei;Guangju Ji
中科院分区：
文献类型：
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作者：
Ji Zheng;Kui Zhai;Yingxiao Chen;Xu Zhang;Lin Miao;Bin Wei;Guangju Ji
摘要平滑肌组织的牵张通过增加钙瞬变来调节收缩，但牵张诱导的钙瞬变的机制尚不清楚。我们发现，机械拉伸和维护的小鼠膀胱平滑肌条和单个肌细胞在30%和18%超出初始长度，分别导致钙振荡。实验结果表明，机械牵张可显著增加肌肉收缩的幅度和持续时间，同时也可增加一氧化氮（NO）的生成。拉伸诱导的Ca 2+振荡和收缩性增加被NO抑制剂L-NAME或eNOS（也称为NOS 3）基因失活完全消除。此外，eNOS敲除的心肌细胞暴露于外源性NO供体诱导Ca 2+振荡。选择性三磷酸肌醇受体（IP 3R）抑制剂xestospongin C可显著抑制牵张诱导的钙振荡，ryanodine可部分抑制牵张诱导的钙振荡。此外，牵张诱导的Ca 2+振荡也被磷酸肌醇3-激酶（PI 3 K）抑制剂LY 294002抑制，但不被可溶性鸟苷酸环化酶（sGC）抑制剂ODQ。这些结果表明，拉伸心肌细胞并维持在一定长度导致Ca 2+振荡，该振荡是NO依赖性的，而不是sGC和cGMP依赖性的，并且是由平滑肌中的PI 3 K激活引起的。总结：肌细胞的拉伸和在拉伸长度的维持导致依赖于NO的Ca 2+振荡，但不依赖于可溶性鸟苷酸环化酶（sGC）或cGMP。这是由于PI 3 K的激活。
ABSTRACT The stretching of smooth muscle tissue modulates contraction through augmentation of Ca2+ transients, but the mechanism underlying stretch-induced Ca2+ transients is still unknown. We found that mechanical stretching and maintenance of mouse urinary bladder smooth muscle strips and single myocytes at 30% and 18% beyond the initial length, respectively, resulted in Ca2+ oscillations. Experiments indicated that mechanical stretching remarkably increased the production of nitric oxide (NO) as well as the amplitude and duration of muscle contraction. Stretch-induced Ca2+ oscillations and contractility increases were completely abolished by the NO inhibitor L-NAME or eNOS (also known as NOS3) gene inactivation. Moreover, exposure of eNOS-knockout myocytes to exogenous NO donor induced Ca2+ oscillations. The stretch-induced Ca2+ oscillations were greatly inhibited by the selective inositol 1,4,5-trisphosphate receptor (IP3R) inhibitor xestospongin C and partially inhibited by ryanodine. Moreover, the stretch-induced Ca2+ oscillations were also suppressed by the phosphoinositide 3-kinase (PI3K) inhibitor LY294002, but not by the soluble guanylyl cyclase (sGC) inhibitor ODQ. These results suggest that stretching myocyte and maintenance at a certain length results in Ca2+ oscillations that are NO dependent , and sGC and cGMP independent, and results from the activation of PI3K in smooth muscle. Summary: Stretching of myocytes and maintenance at the stretched length results in a Ca2+ oscillation that is dependent on NO, but not on soluble guanylyl cyclase (sGC) or cGMP. This results from the activation of PI3K.