乙醇对体外培养的大鼠蓝斑神经元中兴奋性氨基酸受体的抑制作用。

Inhibition by ethanol of excitatory amino acid receptors in rat locus coeruleus neurons in vitro.

作者信息

Nieber K, Poelchen W, Sieler D, Illes P

机构信息

Institut für Pharmazie der Universität, Pharmakologie für Naturwissenschaftler, Leipzig, Germany.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1998 Mar;357(3):299-308. doi: 10.1007/pl00005171.

DOI:10.1007/pl00005171

PMID:9550302

Abstract

Intracellular recordings were made in a pontine slice preparation of the rat brain containing the nucleus locus coeruleus (LC). In a first series of experiments, various parameters of spontaneous action potentials were evaluated. It turned out that ethanol (100 mM) does not alter the firing rate, the spike amplitude and the afterhyperpolarization following a spike. In subsequent experiments, the generation of action potentials was prevented by passing continuous hyperpolarizing current via the recording electrode. Under these conditions, ethanol (100 mM) had no effect on the membrane potential or input resistance. Pressure-applied N-methyl-D-aspartate (NMDA), (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and alpha,beta-methylene ATP (alpha,beta-meATP) reproducibly depolarized LC neurons. While ethanol (100 mM) depressed the NMDA- and AMPA-induced depolarization to a similar extent, it did not interact with alpha,beta-meATP. Lower concentrations of ethanol (10 and 30 mM) had no effect on depolarizing responses to NMDA or AMPA. Noradrenaline applied by pressure pulses reproducibly hyperpolarized LC cells. These hyperpolarizations were unchanged by ethanol (100 mM). Biphasic synaptic potentials consisting of early depolarizing (PSP) and late hyperpolarizing (IPSP) components were evoked by electrical stimulation. Ethanol (100 mM) depressed the PSP and increased the IPSP. Glutamatergic PSPs recorded in the combined presence of picrotoxin (100 microM) and suramin (100 microM) were also inhibited by ethanol (100 mM). However, IPSPs recorded under these conditions were insensitive to ethanol (100 mM). In conclusion, ethanol may interfere with the AMPA (or NMDA) receptor-mediated fraction of the PSP and slightly facilitate the alpha2 adrenoceptor-mediated fraction of the IPSP.

摘要

在包含蓝斑核（LC）的大鼠脑桥切片标本上进行细胞内记录。在第一系列实验中，评估了自发动作电位的各种参数。结果表明，乙醇（100 mM）不会改变放电频率、动作电位幅度以及动作电位后的超极化。在随后的实验中，通过记录电极施加连续的超极化电流来阻止动作电位的产生。在这些条件下，乙醇（100 mM）对膜电位或输入电阻没有影响。压力施加的N-甲基-D-天冬氨酸（NMDA）、（S）-α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和α,β-亚甲基ATP（α,β-meATP）可重复性地使LC神经元去极化。虽然乙醇（100 mM）对NMDA和AMPA诱导的去极化有相似程度的抑制作用，但它与α,β-meATP没有相互作用。较低浓度的乙醇（10和30 mM）对NMDA或AMPA的去极化反应没有影响。压力脉冲施加的去甲肾上腺素可重复性地使LC细胞超极化。这些超极化不受乙醇（100 mM）影响。电刺激诱发了由早期去极化（PSP）和晚期超极化（IPSP）成分组成的双相突触电位。乙醇（100 mM）抑制PSP并增强IPSP。在印防己毒素（100 μM）和苏拉明（100 μM）共同存在的情况下记录的谷氨酸能PSP也受到乙醇（100 mM）的抑制。然而，在这些条件下记录的IPSP对乙醇（100 mM）不敏感。总之，乙醇可能会干扰PSP中由AMPA（或NMDA）受体介导的部分，并略微促进IPSP中由α2肾上腺素能受体介导的部分。