ELECTROMECHANICAL COUPLING IN THE CORONARY ARTERY

提供足够的氧气和代谢前体， 心脏的持续功能严重依赖于足够的 血液供应 与身体的大多数器官不同，心脏几乎提取所有的 从毛细血管血液中获得氧气， 容量 因此，心脏对氧气需求的任何增加， 会立即增加血流量 即使是短暂的中断 血流可导致局部缺血。 通过以下方式了解机制： 因此，调节哪种冠状血管张力是直接重要的 对我们理解心脏的生理学和病理学有很大的帮助。 拟议的研究调查的作用，机电耦合 在控制冠状动脉张力中起作用。 工作假设是 膜电位的变化在改变膜电位中起着重要作用。 血管的收缩活动。 本文中概述的实验 资助计划将研究机电耦合在 冠状动脉收缩和舒张时的情况。 的 实验设计将包括同时测量电 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，将使用全细胞进一步研究 膜片钳技术在离体冠状动脉细胞。 使用Patch 钳位技术，我们将控制膜电流或电位，以确定 涉及机电的通道的特性 偶合器. 收缩将由组胺H1受体启动 激动剂2-（2-氨基乙基）吡啶（AEP），一种强大的收缩刺激， 冠状动脉会导致去极化 具体的主题， 在本申请中考虑的问题包括：1）什么是收缩- AEP的电压关系或整个组织中K+升高？ 2)是什么 几种不同超极化弛豫电压关系 血管扩张剂吗 3)什么样的K+和Ca++通道可以 发现了什么 4)做的特点 这些通道在整体上支持机电耦合的作用 纸巾？ 5)这些通道的特性是否被AEP修改？ 通过 超极化血管扩张剂 通过提供新的见解 收缩的基本基础是在心脏中启动和抑制的， 冠状动脉我们可以帮助了解冠状动脉的原因 痉挛;缺血、心脏综合征和 突然死亡

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.