Inhibition of spontaneous network activity in neonatal hippocampal slices by energy substrates is not correlated with intracellular acidification.
Inhibition of spontaneous network activity in neonatal hippocampal slices by energy substrates is not correlated with intracellular acidification.
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DOI：
10.1111/j.1471-4159.2010.07111.x
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发表时间：
2011-01-01
影响因子：
4.7
通讯作者：
Bregestovski, Piotr
中科院分区：
文献类型：
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作者：
Mukhtarov, Marat;Ivanov, Anton;Bregestovski, Piotr
几种补充葡萄糖的能量底物，包括乳酸盐、丙酮酸盐和β-羟基丁酸盐，可作为神经元的燃料。最近有报道称，这些底物可以显著调节新生脑片的皮层兴奋性。然而，补充能量底物（CES）也可以诱导细胞内的酸化时，外源性添加。因此，CES对新生儿脑切片兴奋性神经元特性的作用可能是细胞能量状态变化或细胞内酸化或两者兼而有之的结果。在这里，我们试图阐明这些可能性，在新生儿海马通过记录神经元的群体活动和监测细胞内的pH值。我们表明，一个自发的网络活动模式，巨大的去极化电位（GDPs），新生儿海马切片暴露于人工脑脊液的特征，强烈抑制CES和这种效果是不太可能引起的微妙的细胞内酸化这些化合物。事实上，在不含HCO（3）的溶液中，更强的细胞内酸化既不抑制GDP频率，也不抑制GDP振幅。因此，神经元能量稳态的调节是乳酸、丙酮酸和β-羟基丁酸对新生儿脑切片中网络兴奋性影响的最可能因素。
Several energy substrates complementary to glucose, including lactate, pyruvate and beta-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 beta-hydroxybutyrate on network excitability in neonatal brain slices.