Takata Toshihiro, Yang Bo, Sakurai Takashi, Okada Yasuhiro, Yokono Koichi
Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Neurosci Res. 2004 Dec;50(4):467-74. doi: 10.1016/j.neures.2004.08.008.
Lactate is considered an alternative substrate that is capable of replacing glucose in maintaining synaptic function in adult neurons. But, we found recently that lactate could be utilized for maintenance of synaptic potentials only after the activation of NMDA and voltage-dependent-calcium channel during glucose deprivation. To clarify more on the relationship between glycolysis and induction of lactate utilization, we tested lower concentration of glucose with hypoxia to induce a relative shortage of anaerobic energy production. Population spikes are not maintained with lactate following hypoxia in 10 mM glucose medium, but are maintained at their original levels with lactate after exposure to hypoxia in lower concentration (5 mM) of glucose. Hypothermia during low glucose-hypoxia, bath application of the NMDA channel blocker and the voltage-sensitive calcium channel blocker, as well as the omission of extracellular calcium prevented the induction of the lactate-supported population spikes. ATP levels in the tissue slices are relatively preserved in the conditions that block the induction of lactate-supported population spikes. From these observations, we propose that the energy source for maintenance of synaptic function in adult neuron changes from adult form (glucose alone) to immature one (glucose and/or lactate) after short of glucose supply.
乳酸被认为是一种替代底物，能够在维持成年神经元突触功能方面取代葡萄糖。但是，我们最近发现，只有在葡萄糖剥夺期间NMDA和电压依赖性钙通道激活后，乳酸才能用于维持突触电位。为了更清楚地阐明糖酵解与乳酸利用诱导之间的关系，我们用低氧测试了较低浓度的葡萄糖，以诱导无氧能量产生的相对短缺。在10 mM葡萄糖培养基中低氧后，群体峰电位不能通过乳酸维持，但在暴露于较低浓度（5 mM）葡萄糖的低氧后，群体峰电位能通过乳酸维持在其原始水平。低葡萄糖-低氧期间的低温、NMDA通道阻滞剂和电压敏感性钙通道阻滞剂的浴用，以及细胞外钙的省略，均阻止了乳酸支持的群体峰电位的诱导。在阻止乳酸支持的群体峰电位诱导的条件下，组织切片中的ATP水平相对保持。从这些观察结果来看，我们提出，在葡萄糖供应不足后，成年神经元中维持突触功能的能量来源从成年形式（仅葡萄糖）转变为不成熟形式（葡萄糖和/或乳酸）。
