1,10-Diaminodecane and 1,12-diaminododecane block NMDA receptor currents by an open channel mechanism

Swaminathan Subramaniam, Sean D. Donevan, Michael A Rogawski

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

In whole-cell recordings from cultured rat hippocampal neurons (VH = -60 mV), 1,10-diaminodecane (DA10) and 1,12-diaminododecane (DA12) produced a concentration-dependent block of NMDA-induced currents (IC50 = 30 and 7 μM, resp.). In contrast, the diamines failed to affect AMPA and kainate currents. The inhibition of NMDA currents was highly voltage-dependent and was substantially relieved at positive holding potentials. In outside-out patches, DA10 and DA12 produced a voltage-dependent flickery block of NMDA-activated single-channel currents. These results indicate that DA10 and DA12 antagonize NMDA responses via an open channel mechanism. DA10 and DA12 have been proposed to be inverse agonists at the spermine facilitatory site on the NMDA receptor. However, the channel blocking effects of the diamines complicate the interpretation of their actions at this site.

Original languageEnglish (US)
Pages (from-to)213-216
Number of pages4
JournalNeuroscience Letters
Volume147
Issue number2
DOIs
StatePublished - Dec 7 1992
Externally publishedYes

Fingerprint

N-Methyl-D-Aspartate Receptors
N-Methylaspartate
Diamines
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Spermine
1,12-dodecamethylenediamine
1,10-diaminodecane
Kainic Acid
Patch-Clamp Techniques
Inhibitory Concentration 50
Neurons

Keywords

  • Diaminodecane
  • Diaminododecane
  • Hippocampal neuron
  • Kainate
  • N-Methyl-d-aspartate
  • Polyamine
  • Voltage-dependent block
  • α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

1,10-Diaminodecane and 1,12-diaminododecane block NMDA receptor currents by an open channel mechanism. / Subramaniam, Swaminathan; Donevan, Sean D.; Rogawski, Michael A.

In: Neuroscience Letters, Vol. 147, No. 2, 07.12.1992, p. 213-216.

Research output: Contribution to journalArticle

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AU - Donevan, Sean D.

AU - Rogawski, Michael A

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N2 - In whole-cell recordings from cultured rat hippocampal neurons (VH = -60 mV), 1,10-diaminodecane (DA10) and 1,12-diaminododecane (DA12) produced a concentration-dependent block of NMDA-induced currents (IC50 = 30 and 7 μM, resp.). In contrast, the diamines failed to affect AMPA and kainate currents. The inhibition of NMDA currents was highly voltage-dependent and was substantially relieved at positive holding potentials. In outside-out patches, DA10 and DA12 produced a voltage-dependent flickery block of NMDA-activated single-channel currents. These results indicate that DA10 and DA12 antagonize NMDA responses via an open channel mechanism. DA10 and DA12 have been proposed to be inverse agonists at the spermine facilitatory site on the NMDA receptor. However, the channel blocking effects of the diamines complicate the interpretation of their actions at this site.

AB - In whole-cell recordings from cultured rat hippocampal neurons (VH = -60 mV), 1,10-diaminodecane (DA10) and 1,12-diaminododecane (DA12) produced a concentration-dependent block of NMDA-induced currents (IC50 = 30 and 7 μM, resp.). In contrast, the diamines failed to affect AMPA and kainate currents. The inhibition of NMDA currents was highly voltage-dependent and was substantially relieved at positive holding potentials. In outside-out patches, DA10 and DA12 produced a voltage-dependent flickery block of NMDA-activated single-channel currents. These results indicate that DA10 and DA12 antagonize NMDA responses via an open channel mechanism. DA10 and DA12 have been proposed to be inverse agonists at the spermine facilitatory site on the NMDA receptor. However, the channel blocking effects of the diamines complicate the interpretation of their actions at this site.

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