MOLECULAR PHYSIOLOGY--CARDIAC MUSCLE

描述：申请人已鉴定出一种新的钾通道基因 (Kv4.3)，在犬和人的脑室中高水平表达。 基于mRNA表达的研究和功能特性分析 在心室肌细胞的瞬时外向电流(Ito) 提示Kv4.3通道是Ito in的主要通道 犬类和人类心肌细胞。这一渠道是决定 心脏活动的持续时间和形状的地区差异 潜力，这促成了一些基本的现象 心电图ST段和T波形态。它 也可能对理解 抗心律失常药物的作用和相互作用。申请者将会 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 在犬的心脏中，以期了解哪一种钾通道 基因对心脏活动的区域分化有贡献 潜力。具体目标是：1)比较生物物理和 自然瞬变Kv4.3通道的药理学特性 犬心脏外向电流(Ito)来验证Kv4.3 阿尔法亚单位本身可以复制天然电流的功能。 2)检测Kv4.3通道蛋白在犬体内的表达分布 心。3)检测不同组织中钾通道基因的表达 确定犬心脏特殊区域的分子基础 这些组织中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.