INSERM-U901, Université de la Méditerranée, Marseille, France.
J Neurochem. 2011 Jan;116(2):316-21. doi: 10.1111/j.1471-4159.2010.07111.x.
Several energy substrates complementary to glucose, including lactate, pyruvate and β-hydroxybutyrate, serve as a fuel for neurons. It was reported recently that these substrates can substantially modulate cortical excitability in neonatal slices. However, complementary energy substrates (CES) can also induce an intracellular acidification when added exogenously. Therefore, action of CES on the neuronal properties governing excitability in neonatal brain slices may be underlain by a change in the cell energy status or by intracellular acidification, or both. Here, we attempt to elucidate these possibilities in neonatal hippocampus by recording neuronal population activity and monitoring intracellular pH. We show that a spontaneous network activity pattern, giant depolarizing potentials (GDPs), characteristic for the neonatal hippocampal slices exposed to artificial cerebrospinal fluid, is strongly inhibited by CES and this effect is unlikely to be caused by a subtle intracellular acidification induced by these compounds. Indeed, a much stronger intracellular acidification in the HCO(3) -free solution inhibited neither the GDP frequency nor the GDP amplitude. Therefore, modulation of neuronal energy homeostasis is the most likely factor underlying the effect of lactate, pyruvate and β-hydroxybutyrate on network excitability in neonatal brain slices.
几种与葡萄糖互补的能量底物，包括乳酸盐、丙酮酸和β-羟丁酸，可作为神经元的燃料。最近有报道称，这些底物可显著调节新生脑片中皮质的兴奋性。然而，当外源性添加这些互补能量底物（CES）时，也会引起细胞内酸化。因此，CES 对控制新生儿脑片中兴奋性的神经元特性的作用可能是由细胞能量状态的变化或细胞内酸化引起的，或者两者兼而有之。在这里，我们试图通过记录神经元群体活动和监测细胞内 pH 值来阐明这些可能性。我们发现，一种自发的网络活动模式，即巨大去极化电位（GDPs），在暴露于人工脑脊液的新生海马片中具有特征性，CES 强烈抑制 GDPs，而这种作用不太可能是由这些化合物引起的细微细胞内酸化引起的。事实上，HCO3- 缺失溶液中更强的细胞内酸化既没有抑制 GDP 的频率也没有抑制 GDP 的幅度。因此，神经元能量稳态的调节是乳酸盐、丙酮酸和β-羟丁酸对新生儿脑片网络兴奋性影响的最可能因素。
