Relationships between the neuronal sodium/potassium pump and energy metabolism. Effects of K+, Na+, and adenosine triphosphate in isolated brain synaptosomes.
Relationships between the neuronal sodium/potassium pump and energy metabolism. Effects of K+, Na+, and adenosine triphosphate in isolated brain synaptosomes.
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DOI：
10.1085/jgp.95.4.591
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发表时间：
1990-04
期刊：
影响因子：
--
通讯作者：
Dagani F
中科院分区：
文献类型：
--
作者：
Erecińska M;Dagani F
在离体大鼠脑突触体上测定了Na/K泵活性与三磷酸腺苷（ATP）产生的关系。通过改变[K+]e，[Na+]i和[ATP]i来调节酶的活性，同时测量突触体氧摄取和乳酸产生。KCl增加呼吸和糖酵解，表观Km约为1 mM，这表明在脑中正常存在的[K+]e为3.3-4 mM时，泵接近饱和。用6-40 mM KCl去极化对哇巴因敏感的O2摄取的影响可以忽略不计，这表明在所涉及的电压下，Na/K ATP酶的活性在很大程度上不依赖于膜电位。增加[Na+]i，另外藜芦定显着增强糖苷可呼吸和乳酸的生产。对支持泵运行所需的ATP合成速率的计算表明，大于90%的能量来自氧化磷酸化。与此一致：（a）哇巴因敏感的Rb/O2比接近12（即，Rb/ATP比值为2）;（B）Amytal抑制线粒体ATP合成导致86 Rb摄取的糖苷依赖性速率降低。对Na和K运动增强时能量产生途径激活机制的分析表明，糖酵解主要是由磷酸果糖激酶活性的增加所刺激的，磷酸果糖激酶活性的增加是通过腺苷酸（AMP）和无机磷酸盐（Pi）浓度的升高以及磷酸肌酸（PCr）浓度的降低来介导的;线粒体ATP生成升高的主要动力是[ATP]/[ADP] [Pi]（或等价物）的下降和随之而来的线粒体内吡啶核苷酸比率[（NAD]m/[NADH]m）的重新调整。钙对丙酮酸脱氢酶的直接刺激似乎是次要的。结论：突触体Na/K泵主要由氧化磷酸化提供能量，[ATP]/[ADP][Pi]下降是导致能量产生增加的主要因素。
The relationships between Na/K pump activity and adenosine triphosphate (ATP) production were determined in isolated rat brain synaptosomes. The activity of the enzyme was modulated by altering [K+]e, [Na+]i, and [ATP]i while synaptosomal oxygen uptake and lactate production were measured simultaneously. KCl increased respiration and glycolysis with an apparent Km of about 1 mM which suggests that, at the [K+]e normally present in brain, 3.3-4 mM, the pump is near saturation with this cation. Depolarization with 6-40 mM KCl had negligible effect on ouabain-sensitive O2 uptake indicating that at the voltages involved the activity of the Na/K ATPase is largely independent of membrane potential. Increases in [Na+]i by addition of veratridine markedly enhanced glycoside-inhibitable respiration and lactate production. Calculations of the rates of ATP synthesis necessary to support the operation of the pump showed that greater than 90% of the energy was derived from oxidative phosphorylation. Consistent with this: (a) the ouabain-sensitive Rb/O2 ratio was close to 12 (i.e., Rb/ATP ratio of 2); (b) inhibition of mitochondrial ATP synthesis by Amytal resulted in a decrease in the glycoside-dependent rate of 86Rb uptake. Analyses of the mechanisms responsible for activation of the energy-producing pathways during enhanced Na and K movements indicate that glycolysis is predominantly stimulated by increase in activity of phosphofructokinase mediated via a rise in the concentrations of adenosine monophosphate [AMP] and inorganic phosphate [Pi] and a fall in the concentration of phosphocreatine [PCr]; the main moving force for the elevation in mitochondrial ATP generation is the decline in [ATP]/[ADP] [Pi] (or equivalent) and consequent readjustments in the ratio of the intramitochondrial pyridine nucleotides [( NAD]m/[NADH]m). Direct stimulation of pyruvate dehydrogenase by calcium appears to be of secondary importance. It is concluded that synaptosomal Na/K pump is fueled primarily by oxidative phosphorylation and that a fall in [ATP]/[ADP][Pi] is the chief factor responsible for increased energy production.