Motin V G, Yasnetsov V V
P. K. Anokhin Research Institute of Normal Physiology, Russian Academy of Medical Sciences, Moscow, Russia.
All-Russian Research Center for Safety of Bioactive Compounds, Staraya Kupavna, Moscow Region, Russia.
Bull Exp Biol Med. 2015 Oct;159(6):704-7. doi: 10.1007/s10517-015-3053-z. Epub 2015 Oct 30.
Removal of Mg2+ ions from perfusion medium provoked epileptiform activity in CA1 field of surviving rat hippocampal slices manifested in generation of extra population spikes. MK-801 (100 μM), a specific non-competitive antagonist to NMDA-receptor complex, prevented this effect. NMDA (20 μM), the specific agonist to this complex, produced no significant effect on the orthodromic population spikes, but when applied at concentrations of 30 or 40 μM, it inhibited them partially (by 21-28%) or almost completely (by 98-99%), correspondingly. Thus, depending on concentration, NMDA can inhibit the synaptic transmission in Schaffer collaterals-hippocampal CA1 pyramidal neurons axis without triggering the epileptiform activity. D-AP5 (50 μM), a competitive antagonist to NMDA-receptor complex, completely prevented the inhibitory effect of NMDA (40 μM). While MK-801 (100 μM) almost completely prevented the inhibitory effect of NMDA, it did not eliminate it when applied after the agonist. Thus, MK-801 can prevent the inhibitory action of NMDA on synaptic transmission in Schaffer collaterals-hippocampal CA1 pyramidal neurons axis via blocking the channel of NMDA-receptor complex, while NMDA exerts its effect only via activation of NMDA receptors.
从灌注培养基中去除镁离子会诱发存活大鼠海马切片CA1区的癫痫样活动，表现为额外群体峰电位的产生。MK-801（100μM）是一种特异性的NMDA受体复合物非竞争性拮抗剂，可阻止这种效应。NMDA（20μM）是该复合物的特异性激动剂，对顺向群体峰电位无显著影响，但当以30或40μM的浓度应用时，它会相应地部分抑制（21%-28%）或几乎完全抑制（98%-99%）。因此，根据浓度不同，NMDA可以抑制海马CA1区锥体细胞轴突中Schaffer侧支的突触传递，而不引发癫痫样活动。D-AP5（50μM）是NMDA受体复合物的竞争性拮抗剂，可完全阻止NMDA（40μM）的抑制作用。虽然MK-801（100μM）几乎完全阻止了NMDA的抑制作用，但在激动剂之后应用时并不能消除这种抑制作用。因此，MK-801可通过阻断NMDA受体复合物通道来阻止NMDA对海马CA1区锥体细胞轴突中Schaffer侧支突触传递的抑制作用，而NMDA仅通过激活NMDA受体发挥其作用。
