Involvement of divalent ions in the nitric oxide-induced blockade of N-methyl-D-aspartate receptors in cerebellar granule cells.
We have previously shown that nitric oxide blocks the N-methyl-D-aspartate (NMDA) receptor without affecting the agonist binding site. We now report that in cerebellar granule cells nitric oxide decreases the NMDA channel conductance and open probability, in voltage-dependent and -independent manners, respectively, by acting on an extracellular site different from the redox, glycine, and pH modulatory sites of the receptor-channel complex. This inhibition is not additive with those of Mg2+ and Zn2+. Moreover, removal of trace concentrations of metal ions in the external medium by means of metal ion-chelators significantly reduced the inhibitory action of nitric oxide on NMDA currents. These results indicate that divalent ions are required for the blockade of NMDA receptors by NO donors.
Fagni
L
L
Mecanismes Moléculaires des Communications Cellulaires, UPR CNRS 9023, Centre CNRS INSERM de Pharmacologie et d'Endocrinologie, Montpellier, France.
Olivier
M
M
Lafon-Cazal
M
M
Bockaert
J
J
D000818:Animals; D002413:Cations, Divalent; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D005998:Glycine / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D016202:N-Methylaspartate / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology*; D010084:Oxidation-Reduction; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D002413:Cations, Divalent; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; C002385:linsidomine; D016202:N-Methylaspartate; D008981:Molsidomine; D005998:Glycine