CALCIUM-DEPENDENT INACTIVATION OF HETEROMERIC NMDA RECEPTOR-CHANNELS EXPRESSED IN HUMAN EMBRYONIC KIDNEY-CELLS

1. Whole-cell currents through heteromeric NR1-NR2A and NR1-NR2B subun it combinations of NMDA channels transiently expressed in human embryo nic kidney cells (HEK 293) were studied using the patch-clamp techniqu e. 2. With 4 mM Mg-ATP in the internal pipette solution, the responses of cells expressing NR1-NR2A channels to glutamate application gradua lly decreased, reaching 50% of control during the first 20 min of reco rding. This process was accompanied by acceleration of desensitization . 3. Conditioning (5-15 s) applications of glutamate (100 mu M) induce d 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 degre e of inactivation and the time constant of recovery increased with the duration of conditioning applications of glutamate, and with an eleva tion of Ca2+ in the external solution. 4. These results show that both NR1-NR2A and NR1-NR2B recombinant NMDA receptor-channels expressed in KEK 293 cells can be transiently inhibited by Ca2+ ions ina similar w ay to that described for hippocampal neurones.