NMDA antagonists and potentiation of NMDA-induced motoneuron depolarizations in the isolated frog spinal cord.
The action of N-methyl-D-aspartate (NMDA) antagonists on motoneurons was studied in the isolated, hemisected frog spinal cord using sucrose gap techniques. NMDA-evoked motoneuron depolarizations were depressed by application of APV, APH, kynurenate, Mg2+ ions, ketamine, and MK-801. Upon returning to normal Ringer's solution after exposure to all antagonists (except MK-801). NMDA responses were significantly potentiated. Kainate- and quisqualate-induced depolarizations were unchanged. The facilitation appeared to result, at least in part, from a direct action on motoneuron membranes since it persisted in the presence of tetrodotoxin which eliminated interneuronal firing. However, indirect actions involving interneurons also contributed to the potentiation because NMDA-evoked changes in K+ release were increased following exposure to NMDA antagonists and return to normal medium. Reduction of temperature (7 degrees C) which should reduce amino acid uptake did not affect results with APV. In addition, desensitization of NMDA responses was not altered by application of APV. The results indicate that NMDA antagonists have complex and long-lasting effects on the function of the NMDA receptor complex.
Zhang
D X
DX
Department of Neurology, University of Miami School of Medicine, FL 33101.
Hackman
J C
JC
Davidoff
R A
RA
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D016291:Dizocilpine Maleate; D004357:Drug Synergism; D005071:Evoked Potentials; D007649:Ketamine / Q000494:pharmacology; D007736:Kynurenic Acid / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D016202:N-Methylaspartate; D011188:Potassium / Q000378:metabolism; D011894:Rana pipiens; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D000596:Amino Acids; D003986:Dibenzocycloheptenes; D001224:Aspartic Acid; D016202:N-Methylaspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D007736:Kynurenic Acid; D014633:Valine; D008274:Magnesium; C031231:2-amino-7-phosphonoheptanoic acid; D011188:Potassium