The effects of polyamine agonists and antagonists on N-methyl-D-aspartate-induced depolarizations of amphibian motoneurons in situ

作者：Hackman John C; Holohean Alice M^*

来源：Brain Research, 2010, 1325: 10-18.

DOI：10.1016/j.brainres.2010.02.025

• Spinal cord
• N-methyl-D-aspartate
• Polyamine
• Motoneuron
• Frog
• mGlu
• ACPD
• 5-hydroxytryptamine
• 5-HT2B
• G-protein coupled receptor

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 me 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. Published by Elsevier B.V.

• 出版日期2010-4-14