Modulation of the NMDA Receptor by Cyanide: Enhancement of Receptor-Mediated Responses
The effect of cyanide on the N-methyl-D-aspartate (NMDA)-stimulated increase in cytosolic free calcium ([Ca ++ ] i ) was studied by microfluorescence in fura-2-loaded cerebellar granule cells. The response to NMDA was enhanced by NaCN over a concentration range of 20 to 100 μM. These concentrations...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 280; no. 3; pp. 1341 - 1348 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.03.1997
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Subjects | |
Online Access | Get full text |
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Summary: | The effect of cyanide on the N-methyl-D-aspartate (NMDA)-stimulated increase in cytosolic free calcium ([Ca ++ ] i ) was studied by microfluorescence in fura-2-loaded cerebellar granule cells. The response to NMDA was enhanced by NaCN over
a concentration range of 20 to 100 μM. These concentrations of NaCN in the absence of NMDA had no effect on basal [Ca ++ ] i . In comparison, NaCN did not affect K + -depolarization-induced [Ca ++ ] i elevation. The NaCN potentiation of NMDA-evoked [Ca ++ ] i elevation was blocked by addition of Mg ++ and by the NMDA receptor antagonists 2-amino-5-phosphono-valeric acid and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohept-5,10-imine
maleate. Pretreatment of the cells with pregnenolone sulfate or arachidonate, known modulators of the NMDA receptor, enhanced
NaCN action. The voltage-sensitive calcium channel blockers nifedepine and diltiazem did not affect the NaCN-induced potentiation.
Additionally, the NaCN action was not altered when tetrodotoxin was used to block Na + channel-mediated glutamate release. In patch-clamp studies, NaCN increased the amplitude and duration of NMDA-stimulated
whole-cell currents. NaCN also enhanced the NMDA receptor response in single-channel patch-clamp experiments. In the outside-out
patch recording configuration, NaCN increased the NMDA receptor channel opening frequency without affecting single-channel
conductance or mean channel open time. These results indicate that cyanide interacts directly with the NMDA receptor channel
complex to enhance receptor-mediated responses. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0022-3565 1521-0103 |