Intramuscular Interstitial Cells of Cajal; ion channels and their modulation by calcium ions and neurotransmitters.

肠道运动障碍以几种方式表现出来，要么是活动过度的模式，要么是活动减少的模式。在正常情况下，肠道运动反映了肌源性，神经元和激素因素之间的平衡，但迄今为止，这种平衡通常是如何实现的还不清楚。该项目将研究一类细胞的特性，其在肌源性和神经控制机制中的重要性仅在过去10年中才被认识到。肠道的肌肉壁由两种不同类型的细胞组成。一组平滑肌细胞含有收缩成分，这些细胞的协调行为导致肠壁收缩，从而确保肠内容物沿着胃肠道的受控通道。另一组细胞，Cajal间质细胞，缺乏收缩成分。最近发现这些细胞中的一组是肠道的起搏细胞，负责肌原性活动的启动。它们产生起搏器波，确保肠道有节奏地收缩。这些细胞中的另一组是密集受神经支配的，它们从神经系统接收信息并将这些信息转化为改变肠道活动的信号。因此，这些细胞在肠道的神经控制中起着关键作用。在许多疾病状态下，已发现Cajal间质细胞的数量减少。然而，我们对这些细胞知之甚少。该项目将首次研究参与神经控制的间质细胞的特性，并确定它们如何执行这些基本功能。

Disorders of gut motility manifest themselves in several ways, as either patterns of hyperactivity or patterns of reduced activity. Under normal conditions gut motility reflects a balance between myogenic, neuronal and hormonal factors but as yet how this balance is normally achieved is not understood. This project will examine the properties of a class of cells, whose importance in both myogenic and neural control mechanisms has only been recognized over the last 10 years. The muscular wall of the gut is made up of two distinct types of cells. One group, smooth muscle cells, contains contractile elements and the coordinated behavior of these cells leads to the contractions of the gut wall, so ensuring the controlled passage of gut contents along the gastrointestinal tract. The other group of cells, Interstitial cells of Cajal, lack contractile elements. One set of these cells have recently been found to be the pacemaker cells of the gut responsible for the initiation of myogenic activity. They generate pacemaker waves which ensure that the gut contracts rhythmically. Another set of these cells are densely innervated, they receive messages from the nervous system and translate these messages into signals which alter the activity of the gut. Thus these cells play a key role in the neural control of the gut. In many disease states, the numbers of interstitial cells of Cajal have been found to be reduced. However as yet we know very little about these cells. This project will, for the first time, examine the properties of the interstitial cells involved in neural control and will determine how they carry out these essential functions.