Corticosteroid Regulation of Ion Channel Conductances and mRNA Levels in Individual Hippocampal CA1 Neurons

Overexposure to corticosteroid hormones is harmful to hippocampal neuronal integrity, likely by perturbation of calcium homeostasis. To identify molecular mechanisms at the single-cell level, we characterized mRNA expression corresponding to voltage- and ligand-gated Ca channels in individual dissoc...

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Veröffentlicht in:The Journal of neuroscience 1998-04, Vol.18 (7), p.2685-2696
Hauptverfasser: Nair, Suresh M, Werkman, Taco R, Craig, Johanna, Finnell, Richard, Joels, Marian, Eberwine, James H
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container_end_page 2696
container_issue 7
container_start_page 2685
container_title The Journal of neuroscience
container_volume 18
creator Nair, Suresh M
Werkman, Taco R
Craig, Johanna
Finnell, Richard
Joels, Marian
Eberwine, James H
description Overexposure to corticosteroid hormones is harmful to hippocampal neuronal integrity, likely by perturbation of calcium homeostasis. To identify molecular mechanisms at the single-cell level, we characterized mRNA expression corresponding to voltage- and ligand-gated Ca channels in individual dissociated CA1 neurons in response to long-term corticosterone (CORT) exposure. Predominant mineralocorticoid receptor occupation (ADC-LO group) resulted in low levels of P/Q- and L-type Ca channel mRNAs, high levels of GluR-2 versus GluR-1, and a high ratio of NMDAR-2A to NMDAR-2B mRNA. Corresponding alterations in protein expression were consistent with the restriction of Ca influx. In contrast, additional glucocorticoid receptor occupation (ADC-HI group) altered the expression of these mRNAs in a manner consistent with enhanced Ca influx; interestingly, qualitatively similar alterations were seen in control ADX neurons. Electrophysiological data from the same neurons indicate that Ca current amplitudes also are modulated by CORT, although on a shorter time scale. Finally, principal components analysis (PCA) suggests that neuronal AMPA and NMDA receptor composition may be regulated by MR and GR activation in a complex manner. Therefore, our data implicate molecular events by which CORT may regulate Ca influx into CA1 hippocampal neurons.
doi_str_mv 10.1523/jneurosci.18-07-02685.1998
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subjects Adrenal Cortex Hormones - pharmacology
Adrenalectomy
Animals
Calcium - metabolism
Calcium Channels - genetics
Calcium Channels - metabolism
Gene Expression - drug effects
Hippocampus - chemistry
Hippocampus - cytology
Ion Channel Gating - physiology
Male
Neurons - drug effects
Neurons - physiology
Patch-Clamp Techniques
Rats
Rats, Sprague-Dawley
Receptors, AMPA - genetics
Receptors, AMPA - metabolism
Receptors, Glucocorticoid - physiology
Receptors, N-Methyl-D-Aspartate - genetics
Receptors, N-Methyl-D-Aspartate - metabolism
RNA, Messenger - metabolism
title Corticosteroid Regulation of Ion Channel Conductances and mRNA Levels in Individual Hippocampal CA1 Neurons
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