ELECTROPHYSIOLOGY OF DEVELOPING HEART CELLS

心脏细胞发育的电生理学

• 批准号: 3343115
• 负责人: NICHOLAS SPERELAKIS
• 金额: $ 14.54万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-07-01 至 1986-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3343115
• 关键词: RNA; angiotensin II; autoradiography; cardiac glycosides; cardiotonic agents; cations; cell differentiation; cyclic nucleoside monophosphate; electron microscopy; electrophysiology; fluorescence microscopy; heart cell; heart contraction; heart innervation; heart pharmacology; histamine; hormones; local anesthetics; mammalian embryology; microelectrodes; microspectrophotometry; muscle stimulant; neurotransmitters; organ culture; radiotracer; sarcolemma; single cell analysis; tissue /cell culture

This project concerns the cellular electrophysiology of cardiac muscle, with emphasis on the membrane electrical properties and nature of the voltage-dependent cation channels. The changes in membrane electrical properties that occur during development of chick and rat hearts and in cell culture will be studied. The parameters examined include K ions permeability, and ultrastructure. We are attempting to learn what factors control membrane differentiation in situ, e.g., whether neurotrophic factors are involved. In answering these questions, young embryonic hearts will be placed in organ culture to determine what factors control membrane electrical differentiation in vitro. In addition, we will trypsin-disperse young and old embryonic hearts and prepare cell cultures (denervated, as monolayers and as spherical reaggregates. We will attempt to define what factors cause some cultured myocardial cells to revert back (partially dedifferentiate) towards the some cultured myocardial cells to revert back (partially dedifferentiate) towards the young embryonic state, whereas other cell cultures retain (or regain) their highly differentiated state. Spherical reaggregate cultures will be characterized with respect to their electrophysiological properties, degree of electrical coupling, and presence of pharmacological receptors. We will also continue to elucidate the properties of myocardial slow channels, including their ionic specificity, activation energy, etc. A search will be made for other agents which either block the slow channels or which make more slow channels become available for voltage activation, and how this is brought about. We will test our hypothesis that phorphorylation of protein constituent of the slow channel, by a cyclic AMP-dependent protein kinase, makes the channel available for voltage activation, and that this is one of the mechanisms by which some positive inotropic agents and neurotransmitters act. We will test whether the peculiar property of myocaridal slow channels, namely energy dependence, serves to protect the heart under adverse conditions of hypoxia or regional ischemia.

该项目涉及心肌的细胞电生理学， 强调膜的电性能和性质， 电压依赖性阳离子通道。 膜电位的变化 在鸡和大鼠心脏发育过程中以及细胞中发生的特性 文化将被研究。 检测的参数包括K离子渗透率， 和超微结构。 我们试图了解是什么因素控制膜 原位分化，例如，是否与神经营养因子有关。 在 为了回答这些问题，年轻的胚胎心脏将被放置在 培养，以确定哪些因素控制膜电分化， 体外 此外，我们将用胰蛋白酶分散年轻和年老的胚胎心脏， 制备细胞培养物（去神经的，作为单层和作为球形再聚集体。 我们将试图确定是什么因素导致一些培养的心肌细胞， 回复（部分去分化）到一些培养的心肌 细胞回复（部分去分化）到年轻的胚胎 而其他细胞培养物保持（或恢复）其高度 差异化国家 球形再聚集体培养物的特征为： 关于它们的电生理特性，电耦合程度， 和药理学受体的存在。 我们也将继续阐明 心肌慢通道的特性，包括它们的离子特异性， 激活能等。搜索将被用于其他代理， 阻塞慢通道或使更多的慢通道变得可用于 电压激活，以及这是如何实现的。 我们将测试我们的假设 慢通道的蛋白质成分的磷酸化， AMP依赖性蛋白激酶，使通道可用于电压 激活，这是一些积极的机制之一， 变力剂和神经递质起作用。 我们将测试这种奇特的 心肌慢通道的特性，即能量依赖性， 在缺氧或局部缺血的不利条件下保护心脏。