Effectiveness of extracellular lactate/pyruvate for sustaining synaptic vesicle proton gradient generation and vesicular accumulation of GABA
Effectiveness of extracellular lactate/pyruvate for sustaining synaptic vesicle proton gradient generation and vesicular accumulation of GABA
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细胞外乳酸/丙酮酸维持突触小泡质子梯度生成和 GABA 囊泡积累的有效性
DOI：
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发表时间：
2006
影响因子：
4.7
通讯作者：
N. Himmelreich
中科院分区：
文献类型：
--
作者：
A. Tarasenko;M. V. Linetska;L. Storchak;N. Himmelreich
在大鼠脑突触体实验中，使用 [3H]GABA 和荧光染料、电位敏感的罗丹明 6G 和 pH 敏感的吖啶橙，研究了细胞外单羧酸丙酮酸和乳酸对突触小泡膜电位、酸化和神经递质填充的影响。在研究吖啶橙在突触体内突触小泡中积累的实验中，单羧酸盐与葡萄糖类似，确保通过可用和回收的囊泡产生囊泡质子梯度，并且丙酮酸表现出最高的功效。质子梯度水平的增加与突触小泡中 [3H]GABA 积累的增加相关，导致胞吐作用扩大并减弱转运蛋白介导的 [3H]GABA 释放。添加到含葡萄糖的培养基中的丙酮酸导致突触体与罗丹明 6G 的更活跃结合，这反映了线粒体膜超极化，并且神经末梢能量代谢的强化导致总 ATP 含量增加约 25%。丙酮酸还延长了神经末梢制剂的代谢能力状态，使线粒体电位和突触小泡质子梯度长期保持在稳定水平。因此，除了葡萄糖之外，细胞外单羧酸丙酮酸和乳酸可以为孤立神经末梢的能量依赖性过程提供足够的支持，从而使神经递质释放和再摄取系统有效发挥作用。
The effects of extracellular monocarboxylates pyruvate and lactate on membrane potentials, acidification and neurotransmitter filling of synaptic vesicles were investigated in experiments with rat brain synaptosomes using [3H]GABA and fluorescent dyes, potential‐sensitive rhodamine 6G and pH‐sensitive acridine orange. In experiments investigating accumulation of acridine orange in synaptic vesicles within the synaptosomes, monocarboxylates, similarly to glucose, ensured generation of the vesicle proton gradient by available and recycled vesicles, and pyruvate demonstrated the highest efficacy. An increase in the level of proton gradient correlated with enhanced accumulation of [3H]GABA in synaptic vesicles and resulted in enlarged exocytosis and attenuated the transporter‐mediated [3H]GABA release. Pyruvate added to glucose‐contained medium caused more active binding of rhodamine 6G by synaptosomes that reflected mitochondrial membrane hyperpolarization, and this intensification of nerve terminal energy metabolism resulted in an increase in total ATP content by ∼25%. Pyruvate also prolonged the state of metabolic competence of nerve terminal preparations, keeping the mitochondrial potential and synaptic vesicle proton gradient at steady levels over a long period of time. Thus, besides glucose, the extracellular monocarboxylates pyruvate and lactate can provide sufficient support of energy‐dependent processes in isolated nerve terminals, allowing effective functioning of neurotransmitter release and reuptake systems.
谷氨酸转运到突触小泡中。
DOI：
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发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Tabb,JS;Kish,PE;VanDyke,R;Ueda,T
通讯作者：
Ueda,T