DYNAMIC CALCIUM REGULATION IN AIRWAY SMOOTH MUSCLE

气道平滑肌的动态钙调节

• 批准号: 6389611
• 负责人: MATHUR S KANNAN
• 金额: $ 22.51万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2003-12-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6389611
• 关键词: ADP ribosylation; acetylcholine; calcium channel; calcium flux; endothelin; respiratory muscles; sarcoplasmic reticulum; smooth muscle; tissue /cell culture

DESCRIPTION: Intracellular Ca2+ ([Ca2+]I) regulates a number of cellular processes in airway smooth muscle (ASM) in response to agonist stimulation. Recent studies from the principal investigator's laboratory indicate that agonists such as acetylcholine (Ach) and endothelin-1 induce [Ca2+]I oscillations in porcine ASM cells that reflect repetitive Ca2+ release through ryanodine receptor (RyR) channels of the sarcoplasmic reticulum (SR). Studies in non-smooth muscle tissue have demonstrated that cyclic ADP ribose (cADPR), metabolite of b-NAD, is a mediator for RyR activation. Preliminary studies related to this proposal also indicate that 1) cADPR is produced in ASM cells following agonist stimulation, 2) cADPR induces SR Ca2+ release through RyR channels, and 3) cADPR and its antagonist modulate agonist-induced [Ca2+]I oscillations. Additional studies also indicate that [Ca2+]I oscillations are frequency modulated in response to increasing agonist concentration as well as by cADPR. Slower Ca2+ -dependent cellular processes such as force production effectively integrate the faster [Ca2+]I oscillations. The overall hypothesis of the proposed studies is that cADPR, by affecting SR Ca2+ release through Ry channels, mediates agonist-induced [Ca2+]I oscillations in porcine ASM cells. The long-term goal of the proposed studies is to understand the signal transduction pathways underlying agonist-induced SR [Ca2+]I release in ASM cells. The proposed studies will determine the [Ca2+]I response to Ach and endothelin-1 stimulation in single ASM cells, and identify the role of cADPR i [Ca2+]I) regulation in ASM cells.

描述：细胞内Ca2+ ([Ca2+]I)调节许多细胞