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首页> 外文期刊>Journal of Neurophysiology >Glycolysis selectively shapes the presynaptic action potential waveform
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Glycolysis selectively shapes the presynaptic action potential waveform

机译：糖酵解选择性地塑造突触前动作电位波形

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摘要

Mitochondria are major suppliers of cellular energy in neurons; however, utilization of energy from glycolysis vs. mitochondrial oxidative phosphorylation (OxPhos) in the presynaptic compartment during neurotransmission is largely unknown. Using presynaptic and postsynaptic recordings from the mouse calyx of Held, we examined the effect of acute selective pharmacological inhibition of glycolysis or mitochondrial OxPhos on multiple mechanisms regulating presynaptic function. Inhibition of glycolysis via glucose depletion and iodoacetic acid (1 mM) treatment, but not mitochondrial OxPhos, rapidly altered transmission, resulting in highly variable, oscillating responses. At reduced temperature, this same treatment attenuated synaptic transmission because of a smaller and broader presynaptic action potential (AP) waveform. We show via experimental manipulation and ion channel modeling that the altered AP waveform results in smaller Ca2+ influx, resulting in attenuated excitatory postsynaptic currents (EPSCs). In contrast, inhibition of mitochondria-derived ATP production via extracellular pyruvate depletion and bath-applied oligomycin (1 mu M) had no significant effect on Ca2+ influx and did not alter the AP waveform within the same time frame (up to 30 min), and the resultant EPSC remained unaffected. Glycolysis, but not mitochondrial OxPhos, is thus required to maintain basal synaptic transmission at the presynaptic terminal. We propose that glycolytic enzymes are closely apposed to ATP-dependent ion pumps on the presynaptic membrane. Our results indicate a novel mechanism for the effect of hypoglycemia on neurotransmission. Attenuated transmission likely results from a single presynaptic mechanism at reduced temperature: a slower, smaller AP, before and independent of any effect on synaptic vesicle release or receptor activity.
机译：线粒体是神经元细胞能量的主要供应商。然而，在神经传递过程中，突触前区中糖酵解与线粒体氧化磷酸化（OxPhos）的能量利用尚不清楚。使用来自Held小鼠花萼的突触前和突触后录音，我们研究了糖酵解或线粒体OxPhos的急性选择性药理抑制作用对调节突触前功能的多种机制的影响。通过葡萄糖耗竭和碘乙酸（1 mM）处理抑制糖酵解，而不是线粒体OxPhos抑制，迅速改变了传递，导致高度可变的振荡响应。在降低的温度下，由于较小和较宽的突触前动作电位（AP）波形，这种相同的处理减弱了突触传递。我们通过实验操作和离子通道建模表明，改变的AP波形导致较小的Ca2 +流入，从而导致兴奋性突触后电流（EPSCs）衰减。相比之下，通过细胞外丙酮酸耗竭和浸浴应用寡霉素（1μM）抑制线粒体衍生的ATP对Ca2 +的流入没有显着影响，并且在相同的时间范围内（最多30分钟）没有改变AP波形，并且所得的EPSC保持不变。因此需要糖酵解，而不是线粒体OxPhos，以维持突触前末端的基础突触传递。我们建议糖酵解酶与突触前膜上的ATP依赖离子泵紧密相关。我们的结果表明低血糖对神经传递的影响的新机制。减弱的传递可能是由单个的突触前机制在降低的温度下产生的：较慢，较小的AP，之前且与对突触小泡释放或受体活性的任何影响无关。

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