Calcium-dependent inactivation of heteromeric NMDA receptor-channels expressed in human embryonic kidney cells.
1. Whole-cell current through heteromeric NR1-NR2A and NR1-NR2B subunit combinations of NMDA channels transiently expressed in human embryonic kidney cells (HEK 293) were studied using the patch-clamp technique. 2. With 4 mM Mg-ATP in the internal pipette solution, the responses of cells expressing NR1-NR2A channels to glutamate application gradually decreased, reaching 50% of control during the first 20 min of recording. This process was accompanied by acceleration of desensitization. 3. Conditioning (5-15 s) applications of glutamate (100 microM) induced a transient inactivation of NR1-NR2A and NR1-NR2B channels (20-40%) with a slow time course of recovery (tau r = 10-60 s). Both the degree of inactivation and the time constant of recovery increased with the duration of conditioning applications of glutamate, and with an elevation of Ca2+ in the external solution. 4. These results show that both NR1-NR2A and NR1-NR2B recombinant NMDA receptor-channels expressed in HEK 293 cells can be transiently inhibited by Ca2+ ions in a similar way to that described for hippocampal neurones.
Medina
I
I
INSERM, Unite 29 Hospital de Port-Royal, Paris, France.
Filippova
N
N
Charton
G
G
Rougeole
S
S
Ben-Ari
Y
Y
Khrestchatisky
M
M
Bregestovski
P
P
D002118:Calcium / Q000502:physiology*; D002460:Cell Line; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D007473:Ion Channels; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D018698:Glutamic Acid; D002118:Calcium