ION CHANNEL FUNCTION IN MYOCARDIAL CELLS FROM INFARCTS

描述（改编自申请人的申请）本更新项目的长期目标是在更多的细胞/亚细胞水平上了解心肌细胞/亚细胞水平上定义的电异常，即冠状动脉闭塞后5天、14天和2个月存活在梗死心脏心外膜边缘区的心肌细胞中定义的电异常。这些异常导致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5天梗塞心脏的心外膜边缘区的中央共同通路相对于标测的折返环路的外周组织分散的细胞中的特定离子电流的功能，2）测定14天和2个月梗塞心脏边缘区分散的细胞的特异性离子电流的功能，3）确定在5天边界区细胞中观察到的Na电流的幅度降低和动力学改变的基础是心脏钠通道在单通道水平上的什么变化，4）确定改变的酪氨酸激酶功能在改变的Ca 2+和K+电流中的作用及其在5天边界区细胞中的药理学，和5）确定延迟整流K+电流在边界区细胞中的功能和药理学，特别是鉴定Kv11.5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区完成。这些研究的结果将提供一个更详细的了解的离子基础上的电重构的细胞存活在愈合和愈合的心脏梗死后，这样做将有助于确定新的分子靶点治疗折返性室性心律失常发生在这些时间。

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.