Potassium channels in gut pacemaking

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性活动。最著名的例子是心脏及其起搏器细胞。鲜为人知的是，胃和肠也有起搏器细胞，即所谓的Cajal间质细胞（ICC），它对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（单个蛋白质：离子通道）水平上发现起搏器细胞膜上的钾离子通道如何表现，从而使适当的起搏器成为可能。这对开发调节运动功能障碍的药物具有重要意义。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。但它有更广泛的含义，因为最近已经确定门静脉和尿道也有ICC起搏器细胞。此外，在研究领域有许多学术和行业职位需要电生理学技能。这个研究项目将提供令人兴奋的学习机会，在一个完善的实验室在电生理学研究的前沿。所使用的技术是最先进的，特别是钙成像和原位贴片夹持的结合，部分是在我们的实验室开发和使用的。

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.