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。最著名的例子是带有起搏细胞的心脏。鲜为人知的是，胃和肠也有起搏细胞，即所谓的卡哈尔间质细胞 (ICC)，它对于蠕动和分割等运动活动至关重要。 我们提出的研究计划涉及在分子（单一蛋白质：离子通道）水平上找出起搏细胞膜中钾离子通道的行为方式，从而使正确的起搏成为可能。这对于开发调节运动功能障碍的药物非常重要。该研究将导致钾通道的详细表征和作用机制，这在很大程度上决定了细胞的兴奋性。但它具有更广泛的影响，因为最近确定门静脉和尿路也有 ICC 起搏细胞。此外，研究中的许多学术和行业职位都需要电生理学技能。该研究计划将在电生理学研究前沿的完善实验室中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组合，并且部分是在我们的实验室首先开发和使用的。