ELECTROPHYSIOLOGY OF DEVELOPING HEART CELLS

这个项目涉及心肌的细胞电生理学， 重点介绍了薄膜的电学性质和性质 电压依赖的阳离子通道。膜电学的变化 鸡和大鼠心脏发育过程中和细胞内的特性 将对文化进行研究。检查的参数包括K离子渗透性， 和超微结构。我们正试图了解是什么因素控制了细胞膜 原位分化，例如，是否涉及神经营养因子。在……里面 回答这些问题，年轻的胚胎心脏将被放置在器官中 培养以确定哪些因素控制了细胞膜的电分化 体外培养。此外，我们将用胰酶分散年轻和年老的胚胎心脏和 准备细胞培养物(去神经，作为单层和球形聚集体)。 我们将尝试确定是什么因素导致一些培养的心肌细胞 向某些培养的心肌逆转(部分去分化) 向年轻胚胎回复(部分去分化)的细胞 国家，而其他细胞培养保留(或恢复)其高度 分化状态。球形重组培养物的特征是 关于它们的电生理特性、电耦合程度、 以及药理受体的存在。我们还将继续澄清 心肌慢通道的特性，包括它们的离子特异性， 活化能等。将搜索符合以下条件的其他试剂 阻止慢速频道或使更多的慢速频道可用于 电压激活，以及这是如何实现的。我们将检验我们的假设 慢通道的蛋白质组分通过环化的磷酸化 AMP依赖的蛋白激酶，使该通道可用于电压 激活，这是一些积极的 肌力调节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，用于 在缺氧或局部缺血的不利条件下保护心脏。

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.