Potassium channels in gut pacemaking

节奏是所有生物体的核心。除此之外，它们是心脏的跳动，大脑神经编码信息的基础，它们调节繁殖周期，更简单，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。大多数起搏细胞产生电节律。这包括细胞电极化的有节奏的下降（有点像电池耗尽），称为去极化。每个去极化周期都涉及起搏细胞中小孔的协调打开，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。这一时期开发的大量抗心律失常药物证明了这一点，用于治疗各种心脏病，这些药物都针对离子通道。尽管已经在肠道中发现了许多离子通道，但尚不清楚哪些离子通道对起搏很重要，如果是的话，它们如何协调。这是复杂的事实，肠道有几个节奏在不同的频率，这是由两组细胞-神经和Cajal间质细胞（ICC）起搏。我们建议研究钾离子通道参与两种肠道节律的起搏-“慢波”和“分钟节律”-这两种节律都是由ICC起搏的。这将为加拿大学生提供电生理学最先进技术的各种经验。它将使加拿大处于心脏起搏器以外的人类起搏器系统研究的最前沿，有利于工程学（人工起搏器）、药理学（药物设计）和健康科学。

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.