CALCIUM REGULATION IN SINGLE AIRWAY SMOOTH MUSCLE CELLS

单气道平滑肌细胞的钙调节

• 批准号: 2232396
• 负责人: JOHN Mark MADISON
• 金额: $ 31.65万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 1998-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2232396
• 关键词: beta adrenergic agent; biological transport; calcium channel; calcium flux; calcium indicator; calcium transporting ATPase; cell membrane; isoproterenol; manganese; muscarinic receptor; muscle cells; muscle pharmacology; potassium channel; respiratory muscles; ryanodine; sarcoplasmic reticulum; smooth muscle; voltage gated channel

DESCRIPTION (Adapted from the applicant's abstract and specific aims): Contraction of airway smooth muscle causes airway obstruction and relaxation of this muscle is the principal action of beta-adrenergic agonists used to treat asthma. Calcium ion is an important second messenger that contributes to the determination of tension in smooth muscle. The application hypothesizes that the cytosol is not homogeneous with respect to calcium concentrations. There are calcium influx pathways into the cell that are not major determinants of (Ca2+)i and, therefore, not major determinants of tension. Both beta-adrenergic and muscarinic agonists stimulate calcium influx at the cell periphery in order to maintain sarcoplasmic reticulum (SR) calcium stores, but the two different agonists have opposite effects on (Ca2+)i. The specific aims are to 1) determine how beta-adrenergic agonists decrease (Ca2+)i; 2) determine whether beta-adrenergic agonists stimulate calcium influx pathways that have minimal effects on (Ca2+)i because of SR uptake refilling processes; 3) during muscarinic stimulation, determine whether the calcium content of the SR regulates calcium influx; 4) during sustained muscarinic stimulation, determine whether calcium influx occurs via multiple pathways, one of which is a minor determinant of (Ca2+)i because of SR uptake and refilling processes; and 5) characterize the detection of calcium at the cell periphery using specific fura-2 AM loading conditions.

描述（根据申请人的摘要和特定目的改编）： 气道平滑肌的收缩会导致气道阻塞和 放松这种肌肉是β-肾上腺素能的主要作用 激动剂用来治疗哮喘。 钙离子是重要的第二 有助于确定平稳张力的使者 肌肉。 应用假设细胞质不是均匀的 关于钙浓度。 有钙涌入 进入细胞的途径不是（Ca2+）I和，， 因此，不是紧张的主要决定因素。 两者都β-肾上腺素和 毒蕈碱激动剂刺激细胞外围的钙涌入 为了维持肌质网（SR）钙存储，但 两种不同的激动剂对（Ca2+）i具有相反的影响。 具体 目的是1）确定β-肾上腺素能激动剂如何减少（Ca2+）I； 2）确定β-肾上腺素能激动剂是否刺激钙涌入 由于SR的吸收，对（Ca2+）i影响最小的途径 补充过程； 3）在毒蕈碱刺激期间，确定是否 the calcium content of the SR regulates calcium influx; 4）期间 持续的毒蕈碱刺激，确定是否发生钙涌入 通过多个途径，其中之一是（Ca2+）i的次要决定因素 由于SR的吸收和补充过程； 5）表征 使用特定的Fura-2 AM在细胞外围检测钙 加载条件。