Premium
Corticosterone acutely prolonged N ‐methyl‐ d ‐aspartate receptor‐mediated Ca 2+ elevation in cultured rat hippocampal neurons
Author(s) -
Takahashi Taiki,
Kimoto Tetsuya,
Tanabe Nobuaki,
Hattori Takaaki,
Yasumatsu Nobuaki,
Kawato Suguru
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.01251.x
Subject(s) - nmda receptor , medicine , endocrinology , hippocampal formation , corticosterone , depolarization , pregnenolone , pregnenolone sulfate , stimulation , receptor , chemistry , biology , steroid , hormone
This work reports the first demonstration that corticosterone (CORT) has a rapid and transient effect on NMDA receptor‐mediated Ca 2+ signaling in cultured rat hippocampal neurons. Using single cell Ca 2+ imaging, CORT and agonists of glucocorticoid receptors were observed to modulate the NMDA receptor‐mediated Ca 2+ signals in a completely different fashion from pregnenolone sulfate. In the absence of steroids, 100 µ m NMDA induced a transient Ca 2+ signal that lasted for 30–70 s in 86.1% of the neurons prepared from postnatal rats (3–5 days old). After pre‐treatment with 0.1–100 µ m CORT for 10–20 min, NMDA induced extremely prolonged Ca 2+ elevation. This prolonged Ca 2+ elevation was terminated by the application of MK‐801 and followed by washing out of CORT. The proportion of CORT‐modulated neurons within the NMDA‐responsive cells increased from 25.1 to 95.5% when the concentration of CORT was raised from 0.1 to 50 µ m . Substitution of BSA‐conjugated CORT produced essentially the same results. When hippocampal neurons were preincubated with 10 µ m cortisol and 1 µ m dexamethasone for 20 min, a very prolonged Ca 2+ elevation was also observed upon NMDA stimulation. The CORT‐prolonged Ca 2+ elevation caused a long‐lasting depolarization of the mitochondrial membrane, as observed with rhodamine 123. In contrast, incubation with 100 µ m pregnenolone sulfate did not considerably alter the time duration of NMDA‐induced transient Ca 2+ elevation, but caused a significant increase in the peak amplitude of Ca 2+ elevation in hippocampal neurons. These results imply that high levels of CORT induce a rapid and non‐genomic prolongation of NMDA receptor‐mediated Ca 2+ elevation, probably via putative membrane surface receptors for CORT in the hippocampal neurons.