Glucocorticoids specifically enhance L-type calcium current amplitude and affect calcium channel subunit expression in the mouse hippocampus.
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 beta4 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.
Chameau
Pascal
P
Swamnerdam Institute for Life Science and Center for NeuroScience, University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam, The Netherlands. pchameau@science.uva.nl
Qin
Yongjun
Y
Spijker
Sabine
S
Smit
August Benjamin
AB
Smit
Guus
G
Joëls
Marian
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000378:metabolism* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
C514350:CACNA1C protein, mouse; C500963:Cacna1b protein, mouse; C485995:Cacna1d protein, mouse; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D005938:Glucocorticoids; D021122:Protein Subunits; D011965:Receptors, Glucocorticoid; D002118:Calcium