ELECTROMECHANICAL COUPLING IN THE CORONARY ARTERY

为人体提供足够的氧气和代谢前体 心脏的持续功能在很大程度上取决于 血液供应。与身体的大多数器官不同，心脏几乎提取了 毛细血管血液中可利用的氧气和最小的厌氧 容量。因此，心脏对氧气需求的任何增加都必须 与之对应的是血流量立即增加。即使是短暂的中断 血液流动可能会导致缺血。对这些机制的理解 因此，调节哪种冠脉血管张力是非常重要的 有助于我们理解心脏的生理学和病理学。 拟议的研究调查了机电耦合的作用 在冠状动脉张力的控制中发挥作用。工作假说是 膜电位的变化在改变细胞周期中起着重要作用 这条血管的收缩活动。这篇文章中概述的实验 格兰特提案将调查机电耦合在 冠状动脉在收缩和松弛过程中。这个 实验设计将包括同时测量电学参数 以及整个组织的收缩活动。此外，细胞基础 对于这些潜在的变化，将使用整个细胞来进一步研究 膜片钳技术在分离的冠状动脉细胞中的应用。使用面片 钳制技术我们将通过控制膜电流或电位来识别 机电工程中涉及的通道特性 耦合。组胺H1受体将启动收缩 激动剂2-(2-氨基乙基)吡啶(AEP)，一种强有力的收缩刺激剂 已知的冠脉会引起去极化。具体的主题 在本申请中考虑的包括：1)什么是收缩- AEP或整个组织中K+升高的电压关系？2)什么是 几种不同超极化的弛豫电压关系 整个组织中的血管扩张剂？3)K+和Ca++通道可以是哪种 在单个冠状动脉细胞中鉴定？4)是否具有 这些通道在整体上支持机电耦合的作用 组织5)这些通道的特性是否被AEP改变？通过 超极化血管扩张剂？通过提供对 开始收缩和抑制收缩的基本基础 我们可能有助于了解冠状动脉形成的原因 痉挛；一种日益公认的导致缺血、心脏综合征和 猝死。

The delivery of sufficient oxygen and metabolic precursors for the continued function of the heart is critically dependent upon a sufficient blood supply. Unlike most organs of the body the heart extracts almost all available oxygen from the capillary blood and has minimal anaerobic capacity. Any increases in oxygen demand by the heart must therefore be met by an immediate increase in blood flow. Even a brief interruption of blood flow can lead to ischemia. An understanding of the mechanisms by which coronary vascular tone is regulated is thus of immediate importance to our understanding of the physiology and pathology of the heart. The proposed study investigates the role which electromechanical coupling plays in the control of coronary arterial tone. The working hypothesis is that changes in membrane potential play a significant role in modifying the contractile activity of this vessel. The experiments outlined in this grant proposal will investigate the role of electromechanical coupling in the coronary artery during contraction and during relaxation. The experimental design will include the simultaneous measurement of electrical and contractile activity in whole tissue. In addition the cellular basis for these potential changes will be further investigated using whole cell patch clamp techniques in isolated coronary artery cells. Using patch clamp techniques we will control membrane current or potential to identify the characteristics of channels which are involved in electromechanical coupling. Contraction will be initiated with the histamine H1 receptor agonist 2-(2-aminoethyl)pyridine (AEP), a powerful contractile stimulus of the coronary artery known to cause depolarization. The specific topics to be considered in this application include: 1) What is the contraction- voltage relationship for AEP or elevated K+ in whole tissue? 2) What is the relaxation-voltage relationship for several different hyperpolarizing vasodilators in whole tissue? 3) What kind of K+ and Ca++ channels can be identified in single coronary artery cells? 4) Do the characteristics of these channels support a role for electromechanical coupling in the whole tissue? 5) Are the characteristics of these channels modified by AEP? by hyperpolarizing vasodilators? By providing new insights into the fundamental basis by which contraction is initiated and inhibited in the coronary artery we may aid in understanding the causes of coronary arterial spasm; an increasingly recognized cause of ischemia, heart syndrome and sudden death.