Potassium channels in gut pacemaking

肠道起搏中的钾通道

• 批准号: 386877-2011
• 负责人: Huizinga, Jan
• 金额: $ 3.28万
• 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: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=529059
• 关键词: Potassium; channels; gut; pacemaking

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.

节奏对于所有生物体都是核心。除其他事项外，它们是心脏的跳动，是大脑神经的信息编码的基础，它们会调节繁殖周期，更平淡地调节繁殖周期，但同样，它们是肠道协调运动所必需的。产生这种节奏的细胞通常称为起搏器。大多数起搏器细胞会产生电节律。这包括细胞的电偏振（有点像电池向下的电池）的节奏减少，称为去极化。去极化的每个循环都涉及起搏器细胞中小孔的协调开口，电动电荷分子（“离子”）可以通过。因此，这些“离子通道”对起搏器机制至关重要。在过去的四十年中，人们对离子渠道的非常亲密的了解已获得。对此的证词是在此期间开发的大量抗心律失常药物，用于治疗各种心脏病，这些抗心脏病均针对离子通道。尽管肠道中已经确定了许多离子通道，但尚不清楚哪一个对起搏至关重要，如果是这样，则它们的坐标方式。肠道在不同频率下具有多种节奏的事实使这一事实变得复杂，这是由两组细胞神经和Cajal（ICC）的间隙细胞节奏的。我们建议研究钾离子通道在两个肠道节律的起搏中的参与 - “慢波”和“微小节奏” - 两者都由ICC节奏。这将为加拿大学生提供电生理学领域的最先进技术的经验。它将使加拿大成为人类起搏器系统研究的最前沿，然后将心脏起搏器与工程（人工起搏器），药理学（药物设计）和健康科学相关。