Role of Ca-activated K channel and Na pump in the regulation of airway smmoth muscle tone.

钙激活钾通道和钠泵在气道平滑肌张力调节中的作用。

• 批准号: 06670632
• 负责人: TAMAOKI Jun
• 金额: $ 1.09万
• 依托单位: Tokyo Women's Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670632/
• 关键词: Airway smooth muscle; Ion channel; Patch clamp; cyclic nucleotide; asthma; Bronchodilator; アセチルコリン; 気道過敏性

1. Muscle contractile and relaxant responsesIsolated bronchial segments were mounted in organ chambers and the contractile responses to acetylcholine and the relaxant responses to various bronchodilating agents were determined in the presence and absence of K channel blockers and ouabain. Acetylcholine-induced contrction was potentiated by charybdotoxin and ouabain, and the relaxant responses to salbutamol, forskolin and nitroprusside were attenuated by these drugs, whereas glibenclamide and apamin had no effect. Thus, Ca-activated K channel and Na pump play roles in the regulation of airway smooth muscle tone by depolarizing membrane potential.2. Accumulation of cyclic nucleotidesIntracellular cyclic nucleotide concentrations were determined in the presence and absence of charybdotoxin and ouabain. Salbutamol and forskolin increased cAMP conctents and nitroprusside increased cGMP contents, and these effects were not altered by charybdotoxin and ouabain, indicating that intracellular cAMP and cGMP directly stimulate Ca-activated K channel and Na pump in airway smooth muscle cells.3. Patch clamp studiesAddition of DBcAMP and DBcGMP each caused single K channel ion current. Therefore, it was confirmed that these cyclic nucleotides produce Ca-activated K channel opening and Na-K-ATPase activation.

1.肌肉收缩和舒张反应将离体支气管段固定在器官室中，在存在和不存在K通道阻断剂和哇巴因的情况下测定对乙酰胆碱的收缩反应和对各种支气管扩张剂的舒张反应。乙酰胆碱诱导的收缩被增强的charybdotoxin和哇巴因，和松弛反应沙丁胺醇，毛喉素和硝普钠衰减这些药物，而格列本脲和apamin没有效果。因此，钙激活的钾通道和钠泵通过去极化膜电位调节气道平滑肌张力.环核苷酸的积累在存在和不存在卡波毒素和哇巴因的情况下测定细胞内环核苷酸浓度。沙丁胺醇和佛司可林增加cAMP含量，硝普钠增加cGMP含量，而蛇毒和哇巴因不改变这种作用，表明细胞内cAMP和cGMP直接刺激气道平滑肌细胞Ca激活的K通道和Na泵.膜片钳研究：加入DBcAMP和DBcGMP均引起单一的K通道离子电流。因此，证实了这些环核苷酸产生Ca激活的K通道开放和Na-K-ATP酶激活。

项目成果

E.Tagaya: "Regulation of airway Cholinergic neurotrausmission by Ca^<2+>-activated K chaunel and Na^+-K^+-a denosine tri phosphatase" Experimeutal Long Research. 21. 683-694 (1995)

E.Tagaya：“Ca ^ 2 -激活的K通道和Na ^ -K ^ -腺苷三磷酸酶调节气道胆碱能神经损伤”实验长期研究。

E.Tagaya et al.: "Regulation of airway cholinergic neurotransmission by Ca^<2+>-activated K^<> channel and Na^+-K^+ adenosinetriphosphatase" Experimental Lung Research. 21. 683-694 (1995)

E.Tagaya等人：“Ca^2-激活的K^<>通道和Na^-K^腺苷三磷酸酶调节气道胆碱能神经传递”实验肺研究。

玉置 淳: "気道平滑筋とカルシウムイオン" Clinical Calcium. 5. 753-757 (1995)

Jun Tamaki：“气道平滑肌和钙离子”临床钙。5. 753-757 (1995)

E. Tagaya: "Regnlation of airway cholinergic neurotransmission by Ca^<2+>-activated K^+channel and Na^+-K^+ adenosine triphosphatase" Experimental Lung Research. 21. 683-694 (1995)

E. Tagaya：“Ca^2-激活的K^通道和Na^-K^三磷酸腺苷对气道胆碱能神经传递的调节”实验肺研究。

J.Tamaoki: "Airway smooth muscle and calcium" Clinical Culcium. 5. 753-757 (1995)

J.Tamaoki：“气道平滑肌和钙”临床钙。