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

1. 通过实验研究豚鼠心室细胞是否具有肿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在低渗刺激下持续被激活。CFTR - C1电流在心肌细胞体积调节中的作用建立了一种新的监测细胞体积变化的可靠方法。通过高速计算机对CCD相机拍摄的显微细胞图像进行连续处理，计算出反映细胞体积的细胞轮廓面积。用这种方法，得到了以下结果：当细胞暴露于低渗溶液时，细胞有明显的肿胀，肾上腺素激活CFTR电流导致渗透膨胀细胞（RVD）的细胞体积减少。在等渗条件下，CFTR电流的激活在细胞体积调节中发挥作用。在外部为5 ~ 10 Mm K的等渗溶液中，CFTR的激活倾向于减少细胞体积，而在40 ~ 140 Mm K时，CFTR的激活倾向于增加细胞体积，这取决于决定细胞膜电位的K浓度。CFTR电流的这些影响可以通过去除外部C1离子、C1通道阻滞剂和乙酰胆碱来抑制。这些发现表明，CFTR电流与跨膜K电流的流动相关联，可以在等渗条件下调节心肌细胞的体积。也可以推断，在各种生理和病理生理条件下，CFTR电流可能调节心肌细胞胞内溶质的含量。因此，明确了两种类型的C1电流在心脏细胞的细胞体积调节中起重要作用。

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.