Nedergaard M, Goldman S A
Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021.
Am J Physiol. 1993 Aug;265(2 Pt 2):R282-9. doi: 10.1152/ajpregu.1993.265.2.R282.
The glycolytic end product lactic acid induced a rapid transient decrease in cytosolic pH in cultured neurons and astrocytes, as measured by microspectrofluorometry using the fluorescent indicator dye 2',7'-bis-(2-carboxyethyl)-5-(and-6) carboxyfluorescein acetoxymethyl ester. Over a physiological range of pH, the initial rate of cellular acidification was a saturable function of the extracellular lactate concentration, suggesting that a saturable transport system mediated lactic acid permeation across the plasma membrane. This transport process displayed stereoselectivity, with a threefold higher rate of intracellular acidification by L-lactic acid than by its D-isomer. Lactic acid-induced acidification occurred in the absence of intracellular ATP, suggesting that transport proceeded independently of the cellular energy charge. These data suggest the existence of a lactic acid carrier in mammalian neuronal and astrocytic plasma membranes, which might serve an acid-scavenging function under conditions of altered pH homeostasis. In the setting of in vivo cerebral ischemia, this carrier may promote the efflux of lactic acid from astrocytes, redistributing it among less metabolically active neurons.
使用荧光指示剂染料2'，7'-双（2-羧乙基）-5-（和-6）羧基荧光素乙酰氧基甲酯通过显微分光荧光测定法测量发现，糖酵解终产物乳酸可使培养的神经元和星形胶质细胞的胞质pH值迅速短暂下降。在生理pH范围内，细胞酸化的初始速率是细胞外乳酸浓度的饱和函数，这表明存在一个饱和转运系统介导乳酸透过质膜。该转运过程具有立体选择性，L-乳酸引起的细胞内酸化速率比其D-异构体高三倍。在细胞内ATP不存在的情况下，乳酸也能引起酸化，这表明转运过程独立于细胞能量状态。这些数据表明，在哺乳动物神经元和星形胶质细胞质膜中存在乳酸载体，在pH稳态改变的情况下，该载体可能具有清除酸的功能。在体内脑缺血的情况下，这种载体可能促进乳酸从星形胶质细胞中流出，将其重新分配到代谢活性较低的神经元中。
