Potassium channels in gut pacemaking

节奏是所有生物的核心。除此之外，它们还控制着心脏的跳动，是大脑中神经编码信息的基础，它们调节着繁殖周期，更平淡无奇，但同样重要的是，它们是肠道协调运动所必需的。产生这种节律的细胞通常被称为起搏器。大多数起搏器细胞产生电节律。这包括细胞电极化的节律性减少（有点像电池耗尽），称为去极化。每一个去极化周期都涉及到起搏器细胞中小孔隙的协调开放，带电分子（“离子”）可以通过这些小孔。因此，这些“离子通道”对起搏器机制至关重要。在过去的四十年里，人们对心脏中的离子通道有了非常深入的了解。证明这一点的是，在此期间，大量的抗心律失常药物被开发出来，用于治疗各种心脏疾病，这些药物都是针对离子通道的。虽然已经在肠道中发现了许多离子通道，但尚不清楚哪一个对心脏起搏器起重要作用，如果起重要作用，它们是如何协调的。肠道有几种不同频率的节律，这些节律由两组细胞——神经和Cajal间质细胞（ICC）来控制，这一事实使情况变得复杂。我们建议研究钾离子通道在两种肠道节律——“慢波”和“分钟节律”——的起搏中的作用，这两种节律都是由ICC来调节的。这将为加拿大学生提供在电生理学的各种最新技术方面的经验。它将使加拿大在心脏起搏器以外的人体起搏器系统的研究方面处于领先地位，对工程学（人工起搏器）、药理学（药物设计）和健康科学都有好处。

Rhythms are central to all living organisms. Among other things they are the beat of the heart, the basis of information coding by nerves in the brain, they regulate breeding cycles and more prosaically, but just as vitally, they are required for the coordinated movement of the gut. The cells that produce such rhythms are often called pacemakers. Most pacemaker cells generate an electrical rhythm. This consists of a rhythmic decrease in the electrical polarization of the cell (sort of like a battery running down) called a depolarization. Each cycle of depolarization involves the coordinated opening of small pores in the pacemaker cell, through which electrically charged molecules ("ions") can pass. These "ion channels" are therefore crucial to the pacemaker mechanism. In the heart a very intimate knowledge of ion channels has been garnered over the last forty years. Testimony to this are the large number of anti-arrhythmic drugs developed over this period, used to treat diverse heart conditions, which are all targeted at ion channels. Though a number of ion channels have been identified in the gut, it is not clear which of these is important to pacemaking and if so, how they coordinate. This is complicated by the fact that the gut has several rhythms at differing frequencies, which are paced by two sets of cells - nerves and the interstitial cells of Cajal (ICC). We propose to study the involvement of potassium ion channels in the pacing of two gut rhythms - the "slow wave" and the "minute rhythm" - both of which are paced by ICC. This will provide Canadian students with experience in a diverse range of state of the art techniques in electrophysiology. It will put Canada in the forefront of research into human pacemaker systems other then the cardiac pacemaker with benefits for engineering (artificial pacemakers), pharmacology (drug design) and the health sciences.