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 language | English (US) |
|---|---|
| Pages (from-to) | 213-216 |
| Number of pages | 4 |
| Journal | Neuroscience Letters |
| Volume | 147 |
| Issue number | 2 |
| DOIs | |
| State | Published - Dec 7 1992 |
| Externally published | Yes |
Fingerprint
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 journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=0026441322&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026441322&partnerID=8YFLogxK
U2 - 10.1016/0304-3940(92)90598-2
DO - 10.1016/0304-3940(92)90598-2
M3 - Article
C2 - 1283458
AN - SCOPUS:0026441322
VL - 147
SP - 213
EP - 216
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 2
ER -