Paredes A, McManus M, Kwon H M, Strange K
Department of Medicine, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Am J Physiol. 1992 Dec;263(6 Pt 1):C1282-8. doi: 10.1152/ajpcell.1992.263.6.C1282.
During plasma hypertonicity brain volume is regulated acutely by electrolyte uptake and chronically by accumulation of organic solutes such as inositol. Cultured rat C6 glioma cells, an astrocyte-like cell line, show a similar pattern of volume control. Volume regulatory accumulation of inositol requires external inositol, indicating that membrane transport plays a central role in this process. The inositol uptake pathway is Na+ dependent and exhibits Michaelis-Menten kinetics. Chronic hypertonic acclimation results in a twofold increase in the maximum velocity of the transporter without changing the Km. Hypertonic stress also results in a 17-fold increase in transporter mRNA. Elevation of mRNA levels precedes activation of the transporter by 4-6 h, suggesting that increased inositol uptake is mediated by synthesis and membrane insertion of new transport proteins. Reacclimation of hypertonic cells to isotonicity causes a rapid reduction of transporter mRNA levels to control levels within 4 h. In contrast, downregulation of transport activity does not begin until between 10 and 24 h after reexposure to isotonicity.
在血浆高渗状态下,脑容量可通过电解质摄取急性调节,并通过肌醇等有机溶质的积累慢性调节。培养的大鼠C6胶质瘤细胞是一种星形胶质细胞样细胞系,表现出类似的容量控制模式。肌醇的容量调节性积累需要外部肌醇,这表明膜转运在这一过程中起核心作用。肌醇摄取途径依赖于Na+,并表现出米氏动力学。慢性高渗适应导致转运体最大速度增加两倍,而Km不变。高渗应激还导致转运体mRNA增加17倍。mRNA水平的升高比转运体激活提前4-6小时,这表明肌醇摄取增加是由新转运蛋白的合成和膜插入介导的。高渗细胞复置于等渗状态会导致转运体mRNA水平在4小时内迅速降至对照水平。相比之下,转运活性的下调直到重新暴露于等渗状态后10至24小时之间才开始。