CORTICOSTEROID REGULATION OF ION-CHANNEL CONDUCTANCES AND MESSENGER-RNA LEVELS IN INDIVIDUAL HIPPOCAMPAL CA1 NEURONS

Overexposure to corticosteroid hormones is harmful to hippocampal neur onal integrity, likely by perturbation of calcium homeostasis. To iden tify molecular mechanisms at the single-cell level, we characterized m RNA expression corresponding to voltage-and ligand-gated Ca channels i n individual dissociated CAI neurons in response to long-term corticos terone (CORT) exposure. Predominant mineralocorticoid receptor occupat ion (ADC-LO group) resulted in low levels of P/Q- and L-type Ca channe l mRNAs, high levels of GluR-2 versus GluR-1, and a high ratio of NMDA R-2A to NMDAR-2B mRNA. Corresponding alterations in protein expression were consistent with the restriction of Ca influx. In contrast, addit ional glucocorticoid receptor occupation (ADC-HI group) altered the ex pression of these mRNAs in a manner consistent with enhanced Ca influx ; interestingly, qualitatively similar alterations were seen in contro l ADX neurons. Electrophysiological data from the same neurons indicat e that Ca current amplitudes also are modulated by CORT, although on a shorter time scale. Finally, principal components analysis (PCA) sugg ests that neuronal AMPA and NMDA receptor composition may be regulated by MR and GR activation in a complex manner. Therefore, our data impl icate molecular events by which CORT may regulate Ca influx into CA1 h ippocampal neurons.