ION CHANNEL FUNCTION IN MYOCARDIAL CELLS FROM INFARCTS

该更新项目的长期目标是在更细胞/亚细胞水平上了解心肌细胞中定义的电异常。细胞/亚细胞水平，在冠状动脉闭塞后5天、14天和2个月存活于梗死心脏心外膜边界带的心肌细胞中定义的电异常。这些异常有助于心肌梗死后发生危及生命的室性心律失常。具体目标如下：1)确定从中央公共通路分散的细胞中特定离子电流的功能与绘制的再入心外膜边缘区中央公共通路与绘制的再入心外膜边缘区周围组织的功能；2)确定从14天和2个月梗死心脏边缘区分散的细胞中特定离子电流的功能；3)来确定心脏钠离子通道的变化水平的单通道下观察减少钠电流的幅值和改变动力学边界区细胞5天,4)确定的角色改变酪氨酸激酶功能改变Ca2 +和K +电流及其边界区细胞药理学在5天,和5)来确定延迟整流K +电流的函数和药理学尤其在边界区细胞识别Kvl1.5通道蛋白。研究将使用冠状动脉闭塞后心脏的全细胞和细胞边界带完成。这些研究的结果将提供一个更详细的了解电重构的离子基础，在愈合和愈合的心脏梗塞后存活的细胞，这样做将有助于确定新的分子靶点，治疗在这段时间发生的可重入性室性心律失常。

Description (Adapted from Applicant's Application) The long-term objective of this renewal project is to understand, at a more cellular/subcellular level, the electrical abnormalities defined in myocytes cellular/subcellular level, the electrical abnormalities defined in myocytes that have survived in the epicardial border zone of the infarcted heart 5 days, 14 days and 2 months post coronary artery occlusion. These abnormalities contribute to the occurrence of life threatening ventricular arrhythmias post myocardial infarction. The specific aims are as follows: 1) to determine the function of specific ionic currents in cells dispersed from the central common pathway versus the peripheral tissues of mapped reentrant the central common pathway versus the peripheral tissues of mapped reentrant circuits of the epicardial border zone of the 5 day infarcted heart, 2) to determine the function of specific ion currents of cells dispersed from the border zone of the 14 day and 2 month infarcted heart, 3) to determine what changes in the cardiac sodium channel at the level of the single channel underlie the observed reduced amplitude and altered kinetics of the Na current in 5 day border zone cells, 4) to determine the role of altered tyrosine kinase function in altered Ca2+ and K+ currents and their pharmacology in 5 day border zone cells, and 5) to determine the function and pharmacology of delayed rectified K+ currents in border zone cells in particular to identify Kvl1.5 channel proteins. Studies will be completed using whole cell and cell border zone of hearts post coronary artery occlusion. The results of these studies will provide a more detailed understanding of the ionic basis of electrical remodeling in cells surviving in the healing and healed hearts post infarction and in so doing will help identify new molecular targets for treatment of reentrant ventricular arrhythmias that occur during these times.