Wakita Masahito, Nagami Hideaki, Takase Yuko, Nakanishi Ryoji, Kotani Naoki, Akaike Norio
Research Division for Clinical Pharmacology, Medical Corporation, Juryokai, Kumamoto Kinoh Hospital, 6-8-1, Yamamuro, Kita-ku, Kumamoto 860-8518, Japan.
Research Division of Neurophysiology, Kitamoto Hospital, 3-7-6, Kawarasone, Koshigaya 343-0821, Japan.
Brain Res Bull. 2015 Aug;117:39-44. doi: 10.1016/j.brainresbull.2015.07.009. Epub 2015 Aug 3.
The acute effects of high-dose Li(+) treatment on glutamatergic and GABAergic transmissions were studied in the "synaptic bouton" preparation of isolated rat hippocampal pyramidal neurons by using focal electrical stimulation. Both action potential-dependent glutamatergic excitatory and GABAergic inhibitory postsynaptic currents (eEPSC and eIPSC, respectively) were dose-dependently inhibited in the external media containing 30-150 mM Li(+), but the sensitivity for Li(+) was greater tendency for eEPSCs than for eIPSCs. When the effects of Li(+) on glutamate or GABAA receptor-mediated whole-cell responses (IGlu and IGABA) elicited by an exogenous application of glutamate or GABA were examined in the postsynaptic soma membrane of CA3 neurons, Li(+) slightly inhibited both IGlu and IGABA at the 150 mM Li(+) concentration. Present results suggest that acute treatment with high concentrations of Li(+) acts preferentially on presynaptic terminals, and that the Li(+)-induced inhibition may be greater for excitatory than for inhibitory transmission.
采用局灶性电刺激,在分离的大鼠海马锥体神经元的“突触小体”标本中研究了高剂量Li(+)处理对谷氨酸能和γ-氨基丁酸能传递的急性影响。在含有30 - 150 mM Li(+)的细胞外介质中,依赖动作电位的谷氨酸能兴奋性和γ-氨基丁酸能抑制性突触后电流(分别为eEPSC和eIPSC)均呈剂量依赖性抑制,但Li(+)对eEPSC的敏感性高于eIPSC。当在CA3神经元的突触后胞体膜中检测Li(+)对由外源应用谷氨酸或γ-氨基丁酸引发的谷氨酸或GABAA受体介导的全细胞反应(IGlu和IGABA)的影响时,在150 mM Li(+)浓度下,Li(+)对IGlu和IGABA均有轻微抑制作用。目前的结果表明,高浓度Li(+)的急性处理优先作用于突触前终末,并且Li(+)诱导的抑制对兴奋性传递的作用可能大于对抑制性传递的作用。