A rapid inhibition of NMDA receptor current by corticosterone in cultured hippocampal neurons.
The stress level of corticosterone (CORT) may enhance the vulnerability of neurons to insult by increasing N-methyl-D-aspartate (NMDA) receptor activity. In this study, we present data showing that CORT could exert an inhibitory effect on NMDA currents in cultured neonatal hippocampal neurons. Extracellular application of 0.1,1,10 and 100 microM CORT significantly reduced the inward current evoked by co-application of NMDA (100 microM). Extracellular application of a membrane-impermeable CORT-BSA (10 microM) maintained the CORT effect. RU38486 (10 microM) failed to block the CORT (1 microM) inhibitory effect. Additionally, intracellular application of CORT (10 microM) showing the lack of effectiveness indicated that a non-genomic mechanism mediated the CORT suppression on NMDA receptors in hippocampal neurons. Furthermore, to elevate the activity of protein kinase A by intracellular 8-Br-cAMP maintained the suppressive effect of CORT on NMDA current. Intracellular blockade of protein kinase A by Rp-cAMP (10 microM) or staurosporine (50 nM) reduced NMDA currents and abolished CORT depression of NMDA currents. These data indicated that NMDA current itself is dependent on protein kinase A (PKA) activity and CORT depression of the current could be PKA-dependent at the same time. The rapid inhibitory effect of the stress level CORT on NMDA current might suggest a protective mechanism for neurons exposed to a transient increase in glucocorticoids.
Liu
Ling
L
Department of Physiology, Second Military Medical University, Shanghai, and Department of Neurology, Jinling Hospital, Nanjing 210002, People's Republic of China.
Wang
Chunan
C
Ni
Xin
X
Sun
Jihu
J
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003345:Corticosterone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D006727:Hormone Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012710:Serum Albumin, Bovine; D015735:Mifepristone; D017868:Cyclic AMP-Dependent Protein Kinases; D019311:Staurosporine; D003345:Corticosterone