Calcineurin upregulates local Ca(2+) signaling through ryanodine receptor-1 in airway smooth muscle cells.
Calcineurin upregulates local Ca(2+) signaling through ryanodine receptor-1 in airway smooth muscle cells.
复制标题
钙调神经磷酸酶通过气道平滑肌细胞中的兰尼定受体 1 上调局部 Ca(2) 信号传导。
DOI：
10.1152/ajplung.00149.2014
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Wang,Yong-Xiao
中科院分区：
文献类型：
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作者：
Savoia,CarloP;Liu,Qing-Hua;Zheng,Yun-Min;Yadav,Vishal;Zhang,Zhen;Wu,Ling-Gang;Wang,Yong-Xiao
Local Ca2+signals (Ca2+sparks) play an important role in multiple cellular functions in airway smooth muscle cells (ASMCs). Protein kinase Cϵ is known to downregulate ASMC Ca2+sparks and contraction; however, no complementary phosphatase has been shown to produce opposite effects. Here, we for the first time report that treatment with a specific calcineurin (CaN) autoinhibitory peptide (CAIP) to block CaN activity decreases, whereas application of nickel to activate CaN increases, Ca2+sparks in both the presence and absence of extracellular Ca2+. Treatment with xestospogin-C to eliminate functional inositol 1,4,5-trisphosphate receptors does not prevent CAIP from inhibiting local Ca2+signaling. However, high ryanodine treatment almost completely blocks spark formation and prevents the nickel-mediated increase in sparks. Unlike CAIP, the protein phosphatase 2A inhibitor endothall has no effect. Local Ca2+signaling is lower in CaN catalytic subunit Aα gene knockout (CaN-Aα−/−) mouse ASMCs. The effects of CAIP and nickel are completely lost in CaN-Aα−/−ASMCs. Neither CAIP nor nickel produces an effect on Ca2+sparks in type 1 ryanodine receptor heterozygous knockout (RyR1−/+) mouse ASMCs. However, their effects are not altered in RyR2−/+or RyR3−/−mouse ASMCs. CaN inhibition decreases methacholine-induced contraction in isolated RyR1+/+but not RyR1−/+mouse tracheal rings. Supportively, muscarinic contractile responses are also reduced in CaN-Aα−/+mouse tracheal rings. Taken together, these results provide novel evidence that CaN regulates ASMC Ca2+sparks specifically through RyR1, which plays an important role in the control of Ca2+signaling and contraction in ASMCs.
