Transmembrane Cl^- Movement in Cardiac Cells and Its Pathophysiological Significance

心肌细胞的跨膜Cl^-运动及其病理生理意义

基本信息

批准号：
03670086
负责人：
NAKAYA Haruaki
金额：
$ 1.28万
依托单位：
School of Medicine, Chiba University (1992)Hokkaido University (1991)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670086/
关键词：
Cl^- Channel Cardiac Cells Hypotonic Swelling Depolarization of the Resting Membrane beta-Adrenergic Stimulation Cl^- Channel Blockers Intracellular Cl^- Activity Intracellular K^+ Activity Cl^ーチャネル遮断薬細胞内K^+活性細胞内Cl^ー活性

项目摘要

Electrophysiological experiments using ion-selective electrodes were conducted to determine whether cell swelling activates Cl^- current and whether the Cl^- current is different from that activated by beta-adrenergic stimulation. When ventricular myocytes isolated from guinea-pig heart were exposed to hyposmotic solution (67 % osmolality) for 5 min, cell width, cell length and calculated cell volume were increased by 9.6*1.4 %, 1.0*0.2 %and 21.6*3.3 %, respectively. The change in size was reversible and returned to the control level with switching back to the isosmotic solution. In isolated guinea-pig papillary muscles, 10-min superfusion of the hyposmotic solution (67% osmolality with constant K^+ concentration) produced decreases in action potential duration and resting membrane potential. In quiescent preparations the hyposmotic solution depolarized the resting membrane by 11.5*0.4 mV, which was significantly inhibited by 4, 4'- diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS, 1 mM) and 4- acetoamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS, 1 mM) but not by anthracene-9-carboxylic acid (9AC, 1 mM). In contrast with the membrane depolarization induced by hypotonic stress, the isoproterenol-induced membrane depolarization from -91.1*1.4 mV to -82.1*1.8 mV and decrease in intracellular Cl^- activity (a^iCl) from 32.1*7.8 mM to 23.1*6.0 mM was effectively inhibited by 1 mM 9AC but not by 1 mM DIDS. In guinea-pig papillary muscles superfusion of the hyposmotic solution decreased a^iCl by 46*5 %, which was significantly greater than the decrease in intracellular K^+ activity (26*3 %). These results suggest that the cell swelling induced by hyposmotic solution may activate DIDS- and SITS-sensitive Cl^- channel, resulting in a depolarization of the resting membrane. The Cl^- channel may be different from that activated by beta-adrenergic stimulation.

使用离子选择性电极进行电生理学实验以确定细胞肿胀是否激活Cl^-电流以及Cl^-电流是否与β-肾上腺素刺激激活的电流不同。当从豚鼠心脏分离的心室肌细胞暴露于低渗溶液(67%渗透压)5分钟时，细胞宽度、细胞长度和计算的细胞体积增加了9.6*1.4%、1.0*0.2%和21.6*3.3%，分别。尺寸的变化是可逆的，并且通过切换回等渗溶液返回到控制水平。在离体豚鼠乳头肌中，低渗溶液（67% 渗透压，恒定 K^+ 浓度）灌注 10 分钟会导致动作电位持续时间和静息膜电位降低。在静态制剂中，低渗溶液使静息膜去极化 11.5*0.4 mV，4, 4'-二异硫氰酸二苯乙烯-2,2'-二磺酸（DIDS，1 mM）和 4-乙酰氨基-4'-异硫氰酸二苯乙烯显着抑制该现象-2,2'-二磺酸（SITS，1 mM）但不是通过蒽-9-甲酸（9AC，1 mM）。与低渗应激引起的膜去极化相反，异丙肾上腺素诱导的膜去极化从-91.1*1.4 mV到-82.1*1.8 mV，细胞内Cl^-活性(a^iCl)从32.1*7.8 mM降低到23.1* 6.0 mM 可被 1 mM 9AC 有效抑制，但不能被 1 mM DIDS 抑制。在豚鼠乳头肌中，低渗溶液的灌注使 a^iCl 降低了 46*5%，这明显大于细胞内 K^+ 活性的降低 (26*3%)。这些结果表明，低渗溶液诱导的细胞肿胀可能激活 DIDS 和 SITS 敏感的 Cl^- 通道，导致静息膜去极化。 Cl - 通道可能与β-肾上腺素能刺激激活的通道不同。