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

Swaminathan Subramaniam; Sean D. Donevan; Michael A Rogawski

doi:10.1016/0304-3940(92)90598-2

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 journal › Article › peer-review

14 Scopus citations

Abstract

In whole-cell recordings from cultured rat hippocampal neurons (V_H = -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 language	English (US)
Pages (from-to)	213-216
Number of pages	4
Journal	Neuroscience Letters
Volume	147
Issue number	2
DOIs	https://doi.org/10.1016/0304-3940(92)90598-2
State	Published - Dec 7 1992
Externally published	Yes

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)

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10.1016/0304-3940(92)90598-2

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

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.",

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

author = "Swaminathan Subramaniam and Donevan, {Sean D.} and Rogawski, {Michael A}",

year = "1992",

month = dec,

day = "7",

doi = "10.1016/0304-3940(92)90598-2",

language = "English (US)",

volume = "147",

pages = "213--216",

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TY - JOUR

T1 - 1,10-Diaminodecane and 1,12-diaminododecane block NMDA receptor currents by an open channel mechanism

AU - Subramaniam, Swaminathan

AU - Donevan, Sean D.

AU - Rogawski, Michael A

PY - 1992/12/7

Y1 - 1992/12/7

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.

KW - Diaminodecane

KW - Diaminododecane

KW - Hippocampal neuron

KW - Kainate

KW - N-Methyl-d-aspartate

KW - Polyamine

KW - Voltage-dependent block

KW - α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate

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JO - Neuroscience Letters

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SN - 0304-3940

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ER -

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

Abstract

Keywords

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