MOLECULAR PHYSIOLOGY--CARDIAC MUSCLE

描述：申请人已鉴定出一种新的钾通道基因 （Kv4.3），其在犬和人心室中以高水平表达。 基于mRNA表达研究和功能特性分析， 瞬时外向电流（Ito）在心室肌细胞，他有 提示Kv4.3通道是Ito的主要通道， 犬和人的肌细胞。 这一渠道是一个重要的决定因素， 心脏活动持续时间和形态的区域差异 潜在的，这有助于这些基本现象，如 心电图中ST段和T波的构型。 它 也可能是相当重要的了解 抗疟疾药物的作用和相互作用。 申请人将 深入研究该通道在犬体内的功能和分布 心 他还将研究其他钾通道基因的分布 为了深入了解钾通道 基因有助于心脏活动的区域分化 潜力 具体目的是：1）比较生物物理和 Kv4.3通道的药理学性质与天然瞬态 外向电流（Ito）在犬心脏测试的假设，Kv4.3 α亚基本身可以复制天然电流的功能。 2)检测犬Kv4.3通道蛋白表达的分布 心 3)检测钾通道基因在不同细胞中的表达 犬心脏的专门区域，以确定 不同的动作电位波形。

DESCRIPTION: The applicant has identified a new potassium channel gene (Kv4.3) that is expressed at high levels in canine and human ventricle. Based on mRNA expression studies and analysis of the functional properties of the transient outward current (Ito) in ventricular myocytes he has suggested that the Kv4.3 channel is the major channel underlying the Ito in canine and human myocytes. This channel is an important determinant of regional differences in the duration and shape of the cardiac action potential, which contribute to such fundamental phenomena as the configuration of the ST segment and the T wave in the electrocardiogram. It is also likely to be of considerable importance for understanding the actions and interactions of antiarrhythmic drugs. The applicant will intensively study the function and distribution of this channel in canine heart. He also will study the distribution of other potassium channel genes in canine heart with a view to gaining insight into which potassium channel genes contribute to the regional differentiation of the cardiac action potential. The specific aims are: 1) Compare the biophysical and pharmacological properties of the Kv4.3 channel with the native transient outward current (Ito) in canine heart to test the hypothesis that the Kv4.3 alpha subunit can, by itself, reproduce the function of the native current. 2) Examine the distribution of Kv4.3 channel protein expression in canine heart. 3) Examine potassium channel gene expression in different specialized regions of canine heart to determine the molecular basis for different action potential waveforms in these tissues.