Relationship of intracellular free Ca2+ concentration and calcium-activated chloride channels of pulmonary artery smooth muscle cells in rats under hypoxic conditions |
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Authors: | Yang Zhao Zhang Zhenxiang Xu Yongjian Li Yaqing Ye Tao |
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Institution: | (1) Respiratory Disease Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, China |
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Abstract: | Summary To investigate the relationship between intracellular free Ca2+ concentration (Ca2+]i) and calcium-activated chloride (ClCB) channels of pulmonary artery smooth muscle cells (PASMCs) in rats under acute and chronic hypoxic conditions, acute hypoxia-induced
contraction was observed in rat pulmonary artery by using routine blood vascular perfusionin vitro. The fluorescence Ca2+ indicator Fura-2/AM was used to observe Ca2+]i of rat PASMCs under normal and chronic hypoxic condition. The effect of ClCB channels on PASMCs proliferation was assessed by MTT assay. The ClCB channel blockers niflumic acid (NFA) and indaryloxyacetic acid (IAA-94) exerted inhibitory effects on acute hypoxia-evoked
contractions in the pulmonary artery. Under chronic hypoxic condition, Ca2+]i was increased. Under normoxic condition, Ca2+]i was (123.63±18.98) nmol/L, and in hypoxic condition, Ca2+]i was (281.75±16.48) nmol/L (P<0.01). Under normoxic condition, Ca2+]i showed no significant change and no effect on ClCB channels was observed (P>0.05 Chronic hypoxia increased Ca2+]i which opened ClCB channels. The NFA and IAA-94 blocked the channels and decreased Ca2+]i from (281.75±16.48) nmol/L to (117.66±15.36) nmol/L (P<0.01). MTT assay showed that under chronic hypoxic condition NFA and IAA-94 decreased the value of absorbency (A value) from
0.459±0.058 to 0.224±0.025 (P<0.01). Hypoxia increased Ca2+]i which opened ClCB channels and had a positive-feedback in Ca2+]i. This may play an important role in hypoxic pulmonary hypertension. Under chronic hypoxic condition, ClCB channel may play a part in the regulation of proliferation of PASMCs.
YANG Zhao, female, born in 1967, Doctor in Charge |
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Keywords: | Ca2+-activated Cl− channels intracellular free Ca2+ concentration pulmonary artery smooth muscle hypoxia |
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