CALCIUM-INDUCED CALCIUM RELEASE & URINARY OBSTRUCTION

描述(改编自申请者摘要)：本项目旨在 探讨膀胱平滑肌特异的兴奋收缩偶联机制 并确定这些过程是否与 已知的收缩功能障碍与慢性尿路梗阻有关 膀胱。特别关注的是潜在的分子机制。 钙诱导膀胱平滑肌细胞钙释放(CICR) 激光扫描共聚焦显微镜和膜片钳方法。钙诱导 钙释放，或细胞内钙离子的释放 钙穿过细胞膜，已被证明在 膀胱肌细胞的兴奋-收缩偶联。有证据表明 这一过程的损害与发生的适应性变化有关 在出口梗阻时的膀胱平滑肌中。我们将确定 正常膀胱肌细胞CICR的生物物理特性 这与在受阻膀胱的肌细胞中观察到的结果进行了比较。淘汰赛 将产生靶向缺失ryanodine受体的小鼠，并 检查CICR过程以确定特定细胞内钙的作用 兴奋-收缩偶联中的通道及其相关调节蛋白 膀胱平滑肌层。

DESCRIPTION (Adapted from the Applicant's Abstract): This project seeks to examine specific excitation-contraction coupling mechanisms in bladder smooth muscle cells, and to determine whether these processes are associated with the contractile dysfunction known to occur with chronic obstruction of the urinary bladder. Particular focus will be on the molecular mechanisms underlying calcium-induced calcium release (CICR) in bladder smooth muscle cells, using laser scanning confocal microscopy and patch clamp methods. Calcium-induced calcium release, or the release of intracellular calcium ions by the influx of calcium across the cell membrane, has been shown to play an important role in excitation-contraction coupling in bladder myocytes. Evidence suggests that impairment of this process is associated with the adaptive changes that occur in bladder smooth muscle during outlet obstruction. We will determine the biophysical characteristics of CICR in normal urinary bladder myocytes and compare that with observations in myocytes from obstructed bladders. Knockout mice with targeted deletions of ryanodine receptors will be generated and the CICR process examined to determine the role of specific intracellular calcium channels and associated modulatory proteins in excitation-contraction coupling of bladder smooth muscle.