RECEPTOR REGULATED CALCIUM ENTRY IN EXOCRINE SECRETION

了解与激活相关的步骤中涉及的细节， 受体与细胞的启动和控制 包括生长和分化在内的功能是一个基本问题 涉及各种重要过程，包括 临床情况。 这些激活途径的一个关键特征是 是细胞内Ca 2+的升高，至少部分是由于 增强Ca 2+从细胞外介质的进入。 的步骤 目前还不知道负责激活该途径的基因。 迄今为止，关于这种机制的辩论集中于根据《公约》 条件产生持续升高[Ca 2 +]。 现在 已知在更多生理条件下[Ca 2 +]响应 经常涉及更复杂的变化，包括振荡波 和[Ca 2 +]的空间局部增加（所谓的“触发区”） Ca 2+进入通常被认为只起很小的作用， 但我们最近的数据显示，情况并非如此。 证据 进一步表明，目前解释Ca 2+控制的模型 在[Ca 2 +]持续升高期间进入不足以 解释了我们在这些过程中观察到的Ca 2+进入的特征 更复杂的[Ca 2 +]反应。 这种复杂的[Ca 2 +]信号是 现在被认为是至关重要的适当激活 有效的外分泌液和蛋白质 腺泡细胞分泌。 我们的目的是研究Ca 2+的作用， 进入[Ca 2 +]振荡和[Ca 2 +]触发区， 细胞的数字荧光成像将 用于获取空间信息， [Ca2+]反应和Ca 2+进入。 此外，结合 光子计数显微荧光法 将用于{cA 2 +]响应的高时间分辨率， 它们与膜电位的关系以及 膜电流 Ca ~（2+）内流的性质和作用分析 在这些复杂的反应中， 细胞中的信号通路。 它还可能允许开发 药理学试剂，可以用来操纵或修改这一点， 临床相关的基础和广泛分布的过程。

Understanding of the details involved in the steps linking activation of receptors on the cell surface with the initiation and control of cell function including growth and differentiation is a fundamental question with implications in a wide variety of improtant processes including clinical situations. A key feature of many of these activation pathways is an elevation of intracellular Ca2+ resulting at least in part from an enhanced entry of Ca2+ from the extracellular medium. The steps responsible for the ectivation of this pathway are presently unknown. To date debate on such mechanisms has focussed on responses under conditions generating a sustained elevation in [Ca2+]. It is now known that under more physiological conditions [Ca2+] responses frequently involve more complex changes including oscillations waves and spatially localized increases in [Ca2+] (so-called 'trigger zones') Ca2+ entry has generally been assumed to play only a minor role in such responses but our recent data suggest this is not so. The evidence further suggests that current models explaining the control of Ca2+ entry during a sustained elevation of [Ca2+] are not adequate to account for the features we have observed for Ca2+ entry during these more complex [Ca2+] responses. Such complex [Ca2+] signals are now believed to be of critical importance in the appropriate activation of mechanisms essential for effective exocrine fluid and protein secretion in acinar cells. Our aim is to investigate the role of Ca2+ entry in [Ca2+] oscillations and [Ca2+] trigger zones and the mechanisms controlling it. Digital fluorescence imaging of cells will be employed to obtain spatial information on the relationships between [Ca2+] responses and Ca2+ entry. In addition combined photoncounting microfluorimetry patch-clampong and flash-photolysis will be used for high temporal resolution of {cA2+] responses and their relationships with membrane potential and the activation of membrane currents. Analysis of the nature and roles of Ca2+ entry in such complex responses will significantly further our understanding of signalling pathways in cells. It may also permit the development of pharmacological agents that can be used to manipulate or modify this funddamental and widely distributed process in clinically relevant ways.