title: Corticosteroid regulation of ion channel conductances and mRNA levels in individual hippocampal CA1 neurons.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Nair
authors.forename: T R
authors.initials: TR
authors.lastname: Werkman
authors.forename: J
authors.initials: J
authors.lastname: Craig
authors.forename: R
authors.initials: R
authors.lastname: Finnell
authors.forename: M
authors.initials: M
authors.lastname: Joëls
authors.forename: J H
authors.initials: JH
authors.lastname: Eberwine
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000315:Adrenalectomy; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology*; D015640:Ion Channel Gating / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism
chemical_list: D000305:Adrenal Cortex Hormones; D015220:Calcium Channels; D012333:RNA, Messenger; D018091:Receptors, AMPA; D011965:Receptors, Glucocorticoid; D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium