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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.

采用离子选择电极进行电生理实验，以确定细胞肿胀是否激活Cl^-电流，以及Cl^-电流是否与β -肾上腺素能刺激激活的Cl^-电流不同。从豚鼠心脏分离的心室肌细胞暴露于低渗溶液（渗透压为67%）5 min后，细胞宽度、细胞长度和计算细胞体积分别增加9.6* 1.4%、1.0* 0.2%和21.6* 3.3%。大小的变化是可逆的，并且在切换回等渗溶液后恢复到控制水平。在离体豚鼠乳头肌中，低渗溶液（67%渗透压，K^+浓度恒定）灌注10分钟后，动作电位持续时间和静息膜电位减少。在静息状态下，低氧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-2,2'-二磺酸（SITS, 1 mM）显著抑制去极化，而蒽-9-羧酸（9AC, 1 mM）对去极化无抑制作用。与低渗胁迫诱导的膜去极化相比，异丙肾上腺素诱导的膜去极化从-91.1*1.4 mV降至-82.1*1.8 mV，细胞内Cl^-活性（a^iCl）从32.1*7.8 mM降至23.1*6.0 mM可被1mm 9AC有效抑制，而1mm DIDS则不能。在豚鼠乳头肌中，低渗液的灌注使a^iCl降低了46* 5%，显著大于细胞内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，导致静息膜的去极化。Cl^-通道可能不同于β -肾上腺素能刺激激活的通道。