Ethanol Inhibition of Recombinant Heteromeric NMDA Channels in the Presence and Absence of Modulators
Ethanol Inhibition of Recombinant Heteromeric NMDA Channels in the Presence and Absence of Modulators
复制标题
存在和不存在调节剂时乙醇对重组异聚 NMDA 通道的抑制
DOI:
10.1046/j.1471-4159.1995.65010140.x
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发表时间:
1995
影响因子:
4.7
通讯作者:
S. Treistman
中科院分区:
文献类型:
--
作者:
B. Chu;V. Anantharam;S. Treistman
Abstract: The NMDA receptor/channel has been shown to be inhibited by ethanol in the clinically relevant range 25–100 mM. We studied heteromeric assemblies (NR1b/NR2) of the NMDA receptor, expressed in oocytes, to address three questions regarding this inhibition, and discovered the following: (1) The inhibition was nearly equivalent when ethanol was coapplied with the agonist, and when ethanol was introduced after steady‐state current was established, suggesting that ethanol does not act by interfering with the activation process of the NMDA receptor. (2) The degree of inhibition was controlled by the NR2 subunit, with both NR2A and NR2B significantly more sensitive to ethanol than NR2C and NR2D. (3) Manipulation of the NMDA receptor with a number of agents that normally modulate it did not alter the degree of inhibition produced by ethanol. The presence of Mg2+ (3 and 12.5 µM), Zn2+ (1 and 10 µM), or the glycine antagonist 7‐chlorokynurenic acid (1.25 or 5 µM), did not alter the ethanol sensitivity of heteromeric (NR1b/NR2A, NR1b/NR2B, NR1b/NR2C) NMDA receptors. Redox modulation of the NMDA receptor by dithiothreitol (2 mM) or 5,5′‐dithiobis(2‐nitrobenzoic acid) (1 mM) also did not alter the degree to which ethanol inhibits NMDA receptors. Taken together, these results indicate that the ethanol sensitivity of native NMDA receptors, which likely exist in heteromeric form, results from actions at a site different from those of known modulators of the receptor.
影响因子:
3.6
作者:
David A. Lynch;N. Anegawa;T. Verdoorn;Dolan B. Pritchett
通讯作者:
David A. Lynch;N. Anegawa;T. Verdoorn;Dolan B. Pritchett
影响因子:
3.6
作者:
K. Williams;A. M. Zappia;D. B. Pritchett;Yu-Min Shen;P. Molinoff
通讯作者:
K. Williams;A. M. Zappia;D. B. Pritchett;Yu-Min Shen;P. Molinoff
影响因子:
4.7
作者:
Woodward,JJ;Blair,R
通讯作者:
Blair,R