Ziskind-Conhaim Lea, Gao Bao-Xi, Hinckley Christopher
Department of Physiology and Center for Neuroscience University of Wisconsin Medical School, Madison, Wisconsin 53706, USA.
J Neurophysiol. 2003 Feb;89(2):806-13. doi: 10.1152/jn.00614.2002.
Recently we have shown that acute ethanol (EtOH) exposure suppresses dorsal root-evoked synaptic potentials in spinal motoneurons. To examine the synaptic mechanisms underlying the reduced excitatory activity, EtOH actions on properties of action potential-independent miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs) were studied in spinal motoneurons of newborn rats. Properties of mEPSCs generated by activation of N-methyl-D-aspartate receptors (NMDARs) and non-NMDA receptors and of mIPSCs mediated by glycine and gamma-aminobutyric acid-A receptors (GlyR and GABA(A)R) were examined during acute exposure to 70 and 200 mM EtOH. In the presence of 70 mM EtOH, the frequency of NMDAR- and non-NMDAR-mediated mEPSCs decreased to 53 +/- 5 and 45 +/- 7% (means +/- SE) of control values, respectively. In contrast, the frequency of GlyR- and GABA(A)R-mediated mIPSCs increased to 138 +/- 15 and 167 +/- 23% of control, respectively. Based on the quantal theory of transmitter release, changes in the frequency of miniature currents are correlated with changes in transmitter release, suggesting that EtOH decreased presynaptic glutamate release and increased the release of both glycine and GABA. EtOH did not change the amplitude or rise and decay times of either mEPSCs or mIPSCs, indicating that the presynaptic changes were not associated with changes in the properties of postsynaptic receptors/channels. Acute exposure to 200 mM EtOH increased mIPSC frequency two- to threefold, significantly higher than the increase induced by 70 mM EtOH. However, the decrease in mEPSC frequency was similar to that observed in 70 mM EtOH. Those findings implied that the regulatory effect of EtOH on glycine and GABA release was dose-dependent. Exposure to the higher EtOH concentration had opposite actions on mEPSC and mIPSC amplitudes: it attenuated the amplitude of NMDAR- and non-NMDAR-mediated mEPSCs to ~80% of control and increased GlyR- and GABA(A)R-mediated mIPSC amplitude by ~20%. EtOH-induced changes in the amplitude of postsynaptic currents were not associated with changes in their basic kinetic properties. Our data suggested that in spinal networks of newborn rats, EtOH was more effective in modulating the release of excitatory and inhibitory neurotransmitters than changing the properties of their receptors/channels.
最近我们发现，急性乙醇（EtOH）暴露会抑制脊髓运动神经元中背根诱发的突触电位。为了研究兴奋性活动降低背后的突触机制，我们在新生大鼠的脊髓运动神经元中研究了EtOH对与动作电位无关的微小兴奋性和抑制性突触后电流（mEPSCs和mIPSCs）特性的影响。在急性暴露于70和200 mM EtOH期间，检测了由N-甲基-D-天冬氨酸受体（NMDARs）和非NMDA受体激活产生的mEPSCs以及由甘氨酸和γ-氨基丁酸-A受体（GlyR和GABA(A)R）介导的mIPSCs的特性。在存在70 mM EtOH的情况下，NMDAR和非NMDAR介导的mEPSCs频率分别降至对照值的53±5%和45±7%（平均值±标准误）。相反，GlyR和GABA(A)R介导的mIPSCs频率分别增加至对照值的138±15%和167±23%。根据递质释放的量子理论，微小电流频率的变化与递质释放的变化相关，这表明EtOH减少了突触前谷氨酸的释放，并增加了甘氨酸和GABA的释放。EtOH并未改变mEPSCs或mIPSCs的幅度、上升时间和衰减时间，这表明突触前的变化与突触后受体/通道的特性变化无关。急性暴露于200 mM EtOH使mIPSC频率增加了两到三倍，显著高于70 mM EtOH引起的增加。然而mEPSC频率的降低与在70 mM EtOH中观察到的相似。这些发现表明EtOH对甘氨酸和GABA释放的调节作用是剂量依赖性的。暴露于较高浓度的EtOH对mEPSC和mIPSC幅度有相反的作用：它将NMDAR和非NMDAR介导的mEPSCs幅度衰减至对照值的约80%，并使GlyR和GABA(A)R介导的mIPSC幅度增加约20%。EtOH引起的突触后电流幅度变化与其基本动力学特性的变化无关。我们的数据表明，在新生大鼠的脊髓网络中，EtOH在调节兴奋性和抑制性神经递质的释放方面比改变其受体/通道的特性更有效。
