Spinal Cord Pharmacology Laboratory, Miami VA Healthcare System, Miami, FL 33125, USA.
Brain Res. 2010 Apr 14;1325:10-8. doi: 10.1016/j.brainres.2010.02.025. Epub 2010 Feb 13.
Polyamines have been found to reduce proton inhibition of isolated N-methyl-D-aspartate (NMDA) channels recorded in vitro. This study examines the role of polyamine modulation of motoneuronal excitation in situ, with an emphasis on possible interactions with NMDA-mediated depolarization of motoneurons and receptor mediated modulation of NMDA receptors by L-glutamate and serotonin (5-HT). Motoneuron membrane potential changes were electrotonically recorded in situ from the ventral root of isolated, hemisected amphibian spinal cords using sucrose gap techniques. The methods provided highly stable recordings (<1.0%) of membrane potential changes upon application of NMDA. Spermine, but not spermidine, enhanced NMDA-induced depolarization of motoneurons with and without Mg(2+) present in the superfusate but had no significant effect on either (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD, an mGLU receptor agonist) or 5-HT2B-G-protein receptor mediated enhancement of Mg(2+) blocked NMDA-induced activity. The polyamine antagonist arcaine or the allosteric modulator ifenprodil had no effect on NMDA-induced changes in motoneuron membrane potentials recorded in situ but blocked the effects of spermine. Synthalin did not block spermine enhancement of NMDA-induced depolarization of motoneurons but mimicked Mg(2+) block of the NMDA channel. The data provide evidence that the proton block of the NMDA receptor is maximized in frog motoneurons in situ and also for a spermine specific polyamine site on native NMDA receptors of motoneurons that can enhance NMDA-induced depolarization when activated. Polyamines do not appear to be constitutively active at the motoneurons recorded since polyamine antagonists had no effect on either membrane depolarization or modulation of NMDA receptors.
多胺已被发现可降低体外分离的 N-甲基-D-天冬氨酸（NMDA）通道的质子抑制作用。本研究检查了多胺对原位运动神经元兴奋的调制作用，重点是 NMDA 介导的运动神经元去极化和 L-谷氨酸和 5-羟色胺（5-HT）介导的 NMDA 受体受体介导的调制与 NMDA 受体介导的调制之间的可能相互作用。使用蔗糖间隙技术原位记录离体半切两栖动物脊髓腹根中的运动神经元膜电位变化。这些方法提供了 NMDA 应用时膜电位变化的高度稳定记录（<1.0%）。精胺而非精脒增强了有或没有超滤液中 Mg2+存在时 NMDA 诱导的运动神经元去极化，但对（1S，3R）-1-氨基环戊烷-1,3-二羧酸（ACPD，mGLU 受体激动剂）或 5-HT2B-G 蛋白受体介导的增强 Mg2+阻断 NMDA 诱导的活性均无显著影响。聚胺拮抗剂阿卡因或变构调节剂ifenprodil 对原位记录的运动神经元膜电位 NMDA 诱导变化无影响，但可阻断精胺的作用。Synthalin 不阻断精胺增强 NMDA 诱导的运动神经元去极化，但模拟了 NMDA 通道的 Mg2+阻断。数据提供的证据表明，在原位青蛙运动神经元中，NMDA 受体的质子阻断作用达到最大，并且 NMDA 受体的精胺特异性多胺位点也具有增强 NMDA 诱导的去极化作用，当被激活时。由于聚胺拮抗剂对膜去极化或 NMDA 受体的调制均无影响，因此聚胺似乎在记录的运动神经元中没有组成型活性。
