Studies on the role of Ttype calcium channels in the cardiovascular system using a specific inhibitor

使用特定抑制剂研究 T 型钙通道在心血管系统中的作用

基本信息

批准号：
18590243
负责人：
TANAKA Hikaru
金额：
$ 2.57万
依托单位：
Toho University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

The T-type calcium channel has different properties and distribution for those of the L-type. It is considered to be involved in various physiological and pathophysiological phenomena such as cardiac automaticity, secretion of various active substances, and is therefore anticipated to be a novel therapeutic target. In the this project, I studied the physiological role of the T-type calcium channel using R (-) -efonidipine, the specific inhibitor I found in my previous studies. Contractile force experiments with isolated murine ventricular tissue revealed that the T-type calcium channel contributes to myocardial contraction in the fetal period but not at adulthood. Activation of the T-type calcium channel was involved in the endothelin- 1-induced positive inotropy. Microelectrode recordings in isolated sinoatrial-node preparations revealed that the T-type calcium channel is involved in the pacemaker depolarization of the mouse and guinea-pig but not in the rabbit, which agreed with earliler data on current density. This indicated that the different contribution of the T-type calcium current to pacemaking underlies species difference in heart rate. As it was shown that the factors which determines heart rate is different among species and the condition of the heart, extension of the present study to hearts from various pathological models may lead to the development of novel pharmacological therapy through regulation of heart rate.

T型钙通道具有不同的L型的特性和分布。它被认为与各种生理和病理生理现象有关，例如心脏自动化，各种活性物质的分泌，因此预计将是一个新型的治疗靶标。在该项目中，我使用R（ - ） - 芬替迪（R（ - ） - 芬迪替汀（我在先前的研究中发现的特定抑制剂）研究了T型钙通道的生理作用。分离的鼠心室组织进行的收缩力实验表明，T型钙通道在胎儿时期有助于心肌收缩，但在成年时不有助于心肌收缩。 T型钙通道的激活参与了内皮素1诱导的阳性障碍。孤立的辛里氏节点制剂中的微电极记录表明，T型钙通道与小鼠和豚鼠的起搏器去极化有关，但在兔子中不涉及，这同意了电流密度的Earliler数据。这表明，T型钙电流对起搏的不同贡献是心率上物种差异的基础。正如所表明的那样，确定心率的因素在物种之间是不同的，心脏状况，从各种病理模型的心脏扩展到心脏的状况可能会导致通过调节心率来发展新型药理治疗。