A rapid inhibition of NMDA receptor current by corticosterone in cultured hippocampal neurons

作者：Liu Ling; Wang Chunan; Ni Xin; Sun Jihu^*

来源：Neuroscience Letters, 2007, 420(3): 245-250.

DOI：10.1016/j.neulet.2007.05.003

• acute effect
• corticosterone
• protein kinase A
• NMDA receptor
• hippocampus
• whole-cell patch clamp

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 mu M CORT significantly reduced the inward current evoked by co-application of NMDA (100 mu M). Extracellular application of a membrane-impermeable CORT-BSA (10 mu M) maintained the CORT effect. RU38486 (10 mu M) failed to block the CORT (I mu M) inhibitory effect. Additionally, intracellular application of CORT (10 mu M) 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 mu M) or staurosporine (50nM) 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.

• 出版日期2007-6-15
• 单位中国人民解放军第二军医大学; 南京大学