Glucocorticoids Specifically Enhance L-Type Calcium Current Amplitude and Affect Calcium Channel Subunit Expression in the Mouse Hippocampus

• Published in: Journal of neurophysiology 2007-01, Vol.97 (1), p.5-14
• Main Authors: Chameau, Pascal, Qin, Yongjun, Spijker, Sabine, Smit, Guus, Joels, Marian
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Calcium Channels, L-Type - drug effects; Calcium Channels, L-Type - genetics; Calcium Channels, L-Type - metabolism; Calcium Channels, N-Type - drug effects; Calcium Channels, N-Type - genetics; Calcium Channels, N-Type - metabolism; Calcium Signaling - drug effects; Calcium Signaling - genetics; Dose-Response Relationship, Drug; Glucocorticoids - metabolism; Glucocorticoids - pharmacology; Hippocampus - drug effects; Hippocampus - metabolism; Male; Membrane Potentials - drug effects; Membrane Potentials - physiology; Mice; Mice, Inbred C57BL; Patch-Clamp Techniques; Protein Subunits - drug effects; Protein Subunits - genetics; Protein Subunits - metabolism; Pyramidal Cells - drug effects; Pyramidal Cells - metabolism; Receptors, Glucocorticoid - agonists; Receptors, Glucocorticoid - antagonists & inhibitors; Receptors, Glucocorticoid - metabolism; Up-Regulation - drug effects; Up-Regulation - genetics
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00821.2006

1 Swamnerdam Institute for Life Science; Center for NeuroScience University of Amsterdam, Amsterdam; and 2 Center for Neurogenomics and Cognitive Research, Vrije Universiteit, Amsterdam, The Netherlands Submitted 7 August 2006; accepted in final form 27 September 2006 Previous studies have shown that corticosterone enhances whole cell calcium currents in CA1 pyramidal neurons, through a pathway involving binding of glucocorticoid receptor homodimers to the DNA. We examined whether glucocorticoids show selectivity for L- over N-type of calcium currents. Moreover, we addressed the putative gene targets that eventually lead to the enhanced calcium currents. Electrophysiological recordings were performed in nucleated patches that allow excellent voltage control. Calcium currents in these patches almost exclusively involve N- and L-type channels. We found that L- but not N-type calcium currents were largely enhanced after treatment with a high dose of corticosterone sufficient to activate glucocorticoid receptors. Voltage dependency and kinetic properties of the currents were unaffected by the hormone. Nonstationary noise analysis suggests that the increased current is not caused by a larger unitary conductance, but rather to a doubling of the number of functional channels. Quantitative real-time PCR revealed that transcripts of the Ca v 1 subunits encoding for the N- or L-type calcium channels are not upregulated in the mouse CA1 area; instead, a strong, direct, and consistent upregulation of the 4 subunit was observed. This indicates that the corticosteroid-induced increase in number of L-type calcium channels is not caused by a simple transcriptional regulation of the pore-forming subunit of the channels. Address for reprint requests and other correspondence: P. Chameau, SILS-CNS, Univ. of Amsterdam, Kruislaan 320, 1098 SM Amsterdam, The Netherlands (E-mail: pchameau{at}science.uva.nl )