权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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.

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氯离子电流，以及氯离子电流是否与刺激β-肾上腺素能激活的氯离子电流不同。低渗液(67%渗透压)作用5min后，细胞宽度增加9.6×1.4%，细胞长度增加1.0×0.2%，计算细胞体积增加21.6×3.3%。大小的变化是可逆的，并在切换回等渗溶液后恢复到对照水平。在豚鼠乳头肌，低渗液(67%渗透压，K~(++)恒定)灌流10分钟，动作电位时程和静息膜电位均缩短。4，4‘-二异硫氰基二苯乙烯-2，2’-二磺酸(DIDS，1 mM)和4-acetoamido-4‘-isothiocyanatostilbene-2，2’-disulfonic酸(SITS，1 mM)对静息膜去极化作用显著，而菲-9-羧酸(9Ac，1 mM)对其无明显抑制作用。与低渗应激引起的膜去极化相比，1mM9AC能有效地抑制异丙肾上腺素引起的膜去极化，使膜去极化从-91.1×1.4 mV降至-82.1×1.8 mV，细胞内氯离子活度(a^ICL)从32.1×7.8 mm降至23.1*6.0 mm，但1 mM DIDS对此无明显影响。在豚鼠乳头肌中，低渗液灌流使a？ICL降低46×5%，明显大于细胞内K~+活性的降低(26？3%)。这些结果表明，低渗溶液引起的细胞肿胀可能激活了DIDS和SIT敏感的氯离子通道，导致静息膜的去极化。氯离子通道可能不同于由β-肾上腺素能刺激所激活的通道。