Adler S
J Clin Invest. 1970 Sep;49(9):1647-55. doi: 10.1172/JCI106382.
Intact rat diaphragms were exposed in vitro to varying CO(2) tensions and bicarbonate concentrations, and the steady-state citrate content of diaphragm muscle was measured to investigate the relationship between metabolism and extracellular pH, P(CO2), and (HCO(3) (-)). In addition, rat hemidiaphragms were incubated with 1,5-citrate-(14)C under different acid-base conditions, and (14)CO(2) production was determined as a measure of citrate oxidation. Acidification of the bathing medium achieved by raising CO(2) tension or lowering (HCO(3) (-)) was associated with a decrease in muscle citrate content. On the other hand, alkalinization of the medium induced by lowering CO(2) tension or raising (HCO(3) (-)) caused tissue citrate content to rise. At a physiologic extracellular pH value of approximately 7.40, citrate content was decreased or normal depending on the CO(2)/HCO(3) (-) combination employed to attain the pH. Under low bicarbonate and low P(CO2) conditions, citrate content was reduced. A similar result was found at external pH values of 7.15, implying that at these two extracellular pH levels (HCO(3) (-)) primarily determines citrate content. When changes in citrate content were compared with intracellular pH data reported earlier using the same intact diaphragm preparation, no simple relation between citrate content and intracellular pH was found. The effect of acidity on citrate content seems related to a change in citrate oxidation since the latter increased progressively with increasing degrees of medium acidity. These results show that cellular metabolism is not a simple function of extracellular pH but is dependent on the particular combination of P(CO2) and bicarbonate employed to achieve the pH value. These studies also suggest that accumulation or disposal of organic acids, such as citric acid, helps to regulate cellular acidity thereby contributing to the cells' defense against external acid-base disorders.
将完整的大鼠膈肌在体外暴露于不同的二氧化碳张力和碳酸氢盐浓度下，测量膈肌肌肉的稳态柠檬酸含量，以研究代谢与细胞外pH、P(CO2)和(HCO3(-))之间的关系。此外，将大鼠半膈肌在不同酸碱条件下与1,5-柠檬酸-(14)C一起孵育，并测定(14)CO2的产生量作为柠檬酸氧化的指标。通过提高二氧化碳张力或降低(HCO3(-))使浴液介质酸化与肌肉柠檬酸含量降低有关。另一方面，通过降低二氧化碳张力或提高(HCO3(-))使介质碱化导致组织柠檬酸含量升高。在生理细胞外pH值约为7.40时，根据用于达到该pH值的CO(2)/HCO(3)(-)组合，柠檬酸含量降低或正常。在低碳酸氢盐和低P(CO2)条件下，柠檬酸含量降低。在外部pH值为7.15时也发现了类似结果，这意味着在这两个细胞外pH水平下，(HCO3(-))主要决定柠檬酸含量。当将柠檬酸含量的变化与早期使用相同完整膈肌制备物报道的细胞内pH数据进行比较时，未发现柠檬酸含量与细胞内pH之间存在简单关系。酸度对柠檬酸含量的影响似乎与柠檬酸氧化的变化有关，因为后者随着介质酸度的增加而逐渐增加。这些结果表明，细胞代谢不是细胞外pH的简单函数，而是取决于用于达到该pH值的P(CO2)和碳酸氢盐的特定组合。这些研究还表明，有机酸（如柠檬酸）的积累或处理有助于调节细胞酸度，从而有助于细胞抵御外部酸碱紊乱。
