In:
Journal of Neurophysiology, American Physiological Society, Vol. 99, No. 4 ( 2008-04), p. 1983-1987
Abstract:
Previous studies had not excluded the possibility that the mechanism by which Xenon (Xe) blocks N-methyl-d-aspartate (NMDA) receptors might be that of an open-channel blocker. We tested this possibility on mutant NMDA receptors carrying an alanine (A) to cysteine (C) mutation located within the SYTANLAAF-motif of the third transmembrane region (TM3). This mutation was shown to yield constitutively open ion channels after modification with a thiol-modifying reagent. We expressed such mutant channels in Neuro2A cells and recorded glutamate (50 μM)-induced currents in the whole cell recording mode. Although Xe (3.5 mM) blocked the currents through the wild-type receptor NR1-1a/NR2A and NR1-1a/NR2B by ∼40% and those through the mutant receptors NR1-1a/NR2A(A650C) or NR1-1a/NR2B(A651C) by ∼30%, it was unable to block the currents through the methane thiosulfonate etyhlammonium-modified mutant receptors. On the other hand, established open-channel blockers of the NMDA receptor such as MK-801 (1 μM) or Mg ions (Mg 2+ ; 1 mM) were able to block these permanently open channels. These results suggest that Xe does not act as a classical open-channel blocker at the NMDA receptor.
Type of Medium:
Online Resource
ISSN:
0022-3077
,
1522-1598
DOI:
10.1152/jn.00631.2007
RVK:
XA 10000 ; XA 552555
Language:
English
Publisher:
American Physiological Society
Publication Date:
2008
detail.hit.zdb_id:
80161-6
detail.hit.zdb_id:
1467889-5
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