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Novel physiological function of cardiac beta-adrenoceptor-dependent chloride channel

心脏β-肾上腺素受体依赖性氯离子通道的新生理功能

基本信息

批准号：
09670047
负责人：
EHARA Tsuguhisa
金额：
$ 1.79万
依托单位：
Saga Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670047/
关键词：
chloride channel CFTR RVD cardiac cell guinea-pig cell-volume regulation cell-swelling

项目摘要

1. C1 channels in ventricular cellsExperiments were performed to investigate whether guinea-pig ventricular cells possess the swelling-activated chloride channels (I_C_1, _s_w_e_l_l). The results showed that, in these preparations, I_C_1, _s_w_e_l_l was consistently activated by hypotonic challenges.2. Role of CFTR C1 current in volume regulation in cardiac cellsA new reliable method was developed to monitor the changes in cell volume. The microscopic cell images taken by a CCD camera were continuously processed by a high-speed computer to calculate the area of cell contour, which reflected the cell volume. With this method, the following results were obtained. When cells were exposed to hypotonic solutions, there was a definite cell-swelling, and activation of CFTR current by adrenaline produced a decrease of cell volume in the osmotically inflated cells (RVD). The activation of CFTR current was found to play a role in the cell-volume regulation even under isotonic conditions. In isotonic solutions with external 5 to 10 Mm K, activation of CFTR tended to decrease the cell volume, whereas at 40 to 140 mM K it increased the cell volume depending on the K concentration which determined the cell membrane potential. These effects of CFTR current were inhibited by removal of external C1 ions, C1 channel blockers, and acetylcholine. These findings indicate that CFTR current, in association with the flow of transmembrane K currents, can regulate the volume of cardiac cells under isotonic conditions. It can also be inferred that CFTR current may regulate the content of intracellular solutes in cardiac cells under various physiological and pathophysiological conditions.Thus, it has been clarified that two types of C1 current play an important role in the regulation of cell volume in cardiac cells.

1.本实验观察了豚鼠心室肌细胞是否具有膨胀激活的氯离子通道（I_C_1，_s_w_e_l_l）。结果表明，在这些制剂中，I_C_1，_s_w_e_l_l在低渗刺激下均被激活. CFTR C1电流在心肌细胞容积调节中的作用建立了一种新的可靠的方法来监测细胞容积的变化。用CCD摄像机拍摄显微细胞图像，经高速计算机连续处理，计算细胞轮廓面积，反映细胞体积。采用该方法，获得了以下结果。当细胞暴露于低渗溶液中时，有一定的细胞肿胀，肾上腺素激活CFTR电流，导致膨胀细胞（RVD）的细胞体积减小。CFTR电流的激活被发现甚至在等渗条件下在细胞体积调节中发挥作用。在等渗溶液与外部5至10毫米K，激活CFTR往往会减少细胞体积，而在40至140毫米K，它增加了细胞体积取决于K浓度，确定细胞膜电位。CFTR电流的这些影响被抑制去除外部C1离子，C1通道阻滞剂，和乙酰胆碱。这些发现表明，CFTR电流，与跨膜K电流的流动，可以调节等渗条件下的心肌细胞的体积。同时也可推测CFTR电流在各种生理和病理条件下可调节心肌细胞内溶质的含量，从而阐明了两种类型的C1电流在心肌细胞体积调节中的重要作用。