Potassium channels in gut pacemaking

肠道起搏中的钾通道

• 批准号: 386877-2010
• 负责人: Huizinga, Jan
• 金额: $ 2.91万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2010
• 资助国家: 加拿大
• 起止时间: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=463973
• 关键词: Potassium; channels; gut; pacemaking

In cell biology, one of the most exciting questions is how cells produce spontaneous rhythmic activity. The best-known example is the heart with its pacemaker cells. Lesser known is the fact that the stomach and intestine also have pacemaker cells, so called interstitial cells of Cajal (ICC) which are crucial for motor activity such as peristalsis and segmentation. Our proposed research program deals with finding out at a molecular (single protein: ion channel) level, how the potassium ion channels in the membrane of the pacemaker cells behave so that proper pacemaking is possible. This is important for development of pharmaceuticals to adjust disorders of motor functions. The research will lead to a detailed characterization and mechanism of action of the potassium channels, which determine to a large extent the excitability of the cells. But it has much wider implications because it has recently been established that the portal vein and the urinary tract also have ICC pacemaker cells. Furthermore, there are many academic and industry positions in research that require skills in electrophysiology. This research program will provide exciting learning opportunities in a well-established laboratory at the forefront of electrophysiology research. The techniques used are state of the art, in particular the combination of calcium imaging and in situ patch clamping, and in part developed and used first in our laboratory.

在细胞生物学中，最令人兴奋的问题之一是细胞如何产生自发的节律活动。最著名的例子是心脏和起搏器细胞。鲜为人知的是，胃和肠道也有起搏细胞，即所谓的卡哈尔间质细胞(ICC)，它对蠕动和节段性运动等运动至关重要。我们建议的研究计划涉及在分子(单一蛋白质：离子通道)水平上发现起搏细胞膜上的钾离子通道如何工作，从而使适当的起搏成为可能。这对于开发调整运动功能障碍的药物具有重要意义。这项研究将导致钾通道的详细特征和作用机制，钾通道在很大程度上决定了细胞的兴奋性。但它的意义要广泛得多，因为最近发现门静脉和尿路也有ICC起搏细胞。此外，在研究中有许多学术和行业职位需要电生理学方面的技能。这项研究计划将在一个处于电生理学研究前沿的完善的实验室提供令人兴奋的学习机会。所使用的技术是最先进的，特别是钙成像和原位膜片钳的结合，部分是在我们实验室首次开发和使用的。