|Budget Amount *help
¥2,800,000 (Direct Cost : ¥2,800,000)
Fiscal Year 1998 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1997 : ¥2,000,000 (Direct Cost : ¥2,000,000)
1. C1 channels in ventricular cells
Experiments 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 cells
A 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.