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The Journal of Neuroscience, April 1, 1998, 18(7):2685-2696

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

Suresh M. Nair¹, Taco R. Werkman³, Johanna Craig⁴, Richard Finnell⁴, Marian Joëls³, and James H. Eberwine^{1, 2}

Departments of ¹ Pharmacology and ² Psychiatry, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, ³ Department of Experimental Zoology, University of Amsterdam, 1098 SM Amsterdam, The Netherlands, and ⁴ Department of Veterinary Anatomy and Public Health, College of Veterinary Medicine, Texas Agriculture and Mining University, College Station, Texas 77843-4458

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.

Key words: corticosterone; dissociated CA1 Neurons; aRNA amplification; expression profile; mRNA; ion channels; hippocampus

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Copyright © 1998 Society for Neuroscience  0270-6474/98/1872685-12$05.00/0

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