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Relations Between Intracellular Ions and Energy Metabolism Under Acidotic Conditions: A Study with Nigericin in Synaptosomes, Neurons, and C6 Glioma Cells
Author(s) -
Erecińska Maria,
Nelson David,
Dagani Fiorenzo,
Deas Judith,
Silver Ian A.
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb13629.x
Subject(s) - nigericin , intracellular , glioma , chemistry , metabolism , ion , biophysics , biochemistry , neuroscience , biology , membrane , cancer research , organic chemistry
Effects of nigericin were investigated in rat brain synaptosomes, cultured neurons, and C6 glioma cells to characterize the relations among ATP synthesis, [Na + ] i ., [K + ] i , and [Ca 2+ ] i , and pH under conditions when [H + ] i is substantially increased and transmembrane electrical potential is decreased. Intracellular acidification and loss of K + were accompanied by enhanced oxygen consumption and lactate production and a decrease in cellular energy level. Changes in the last three parameters were attenuated by addition of 1 mM ouabain. In synaptosomes treated with nigericin, neither respiration nor glycolysis was affected by 0.3 μM tetrodotoxin, whereas 1 mM amiloride reduced lactate production by 20% but did not influence respiration. In C6 cells, amiloride decreased the nigericin‐stimulated rate of lactate generation by about 50%. The enhancement by nigericin of synaptosomal oxygen uptake and glycolytic rate decreased with time. However, there was only a small reduction in respiration and none in glycolysis in C6 cells. Measurements with ion‐selective microelectrodes in neurons and C6 cells showed that nigericin also caused a rise in [Ca 2+ ], and [Na + ]., The increase in [Na + ], in C6 cells was partially reversed by 1 mM amiloride. It is concluded that nigericin‐induced loss of K + and subsequent depolarization lead to an increase in Na + influx and stimulation of the Na + /K + pump with a consequent rise in energy utilization; that acidosis inhibits mitochondrial ATP production; that a rise in [H + ] does not decrease glycolytic rate when the energy state (a fall in [ATP] and rises in [ADP] and [AMP]) is simultaneously reduced; that a fall in [K + ], depresses both oxidative phosphorylation and glycolysis; and that the nigericin‐induced alterations in ion levels and activities of energy‐producing pathways can explain some of the deleterious effects of ischemia and hypoxia.