Gullans S R, Kone B C, Avison M J, Giebisch G
Renal Division, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Am J Physiol. 1988 Dec;255(6 Pt 2):F1170-7. doi: 10.1152/ajprenal.1988.255.6.F1170.
Succinate, a dicarboxylic acid, is an intermediate in the Krebs cycle that is transported and metabolized by the renal proximal tubule. It is also known to increase proximal tubule transport of phosphate and glucose but not fluid by unknown mechanisms. In the present study, succinate increased proximal tubule respiration in a dose-dependent manner, and a kinetic evaluation indicated that two separate processes were activated. A lower-affinity (Km = 0.9 mM), higher-capacity stimulation (Vmax increase of 49%) was attributed to a decrease in the mitochondrial coupling efficiency. A higher-affinity process (Km = 0.012 mM) was related to an apparent increase in ATP synthesis. The apparent increase in ATP synthesis was not associated with a change in Na+-K+-ATPase activity, however, but rather indicated a 49% increase in ion transport-independent ATP utilization. Basolateral membrane potential hyperpolarized by -7 mV in the presence of succinate, and this was related to an increase in the K+ transference number. Finally, 1 and 5 mM succinate promoted a net cellular uptake of K+, leading to an 11% increase in intracellular K+, which was not the result of an increase in Na+-K+-ATPase activity. Thus the cellular entry and metabolism of succinate promotes multiple changes in ion transport without altering Na+-K+-ATPase activity.
琥珀酸是一种二羧酸，是三羧酸循环的中间产物，可被近端肾小管转运和代谢。已知它还能增加近端肾小管对磷酸盐和葡萄糖的转运，但对液体转运的影响机制不明。在本研究中，琥珀酸以剂量依赖的方式增加近端肾小管呼吸，动力学评估表明有两个独立的过程被激活。低亲和力（Km = 0.9 mM）、高容量刺激（Vmax增加49%）归因于线粒体偶联效率的降低。高亲和力过程（Km = 0.012 mM）与ATP合成的明显增加有关。然而，ATP合成的明显增加与钠钾ATP酶活性的变化无关，而是表明离子转运非依赖性ATP利用增加了49%。在琥珀酸存在的情况下，基底外侧膜电位超极化了7 mV，这与钾离子转移数的增加有关。最后，1 mM和5 mM的琥珀酸促进了细胞对钾离子的净摄取，导致细胞内钾离子增加了11%，这不是钠钾ATP酶活性增加的结果。因此，琥珀酸的细胞内进入和代谢促进了离子转运的多种变化，而不改变钠钾ATP酶活性。
