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Regulation of CaV3.1 Channels by Glucocorticoids

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Abstract

The activity of low voltage-activated Ca2+ (CaV3) channels is tightly coupled to neurotransmitter and hormone secretion. Previous studies have shown that CaV3 channels are regulated by glucocorticoids (GCs), though the mechanism underlying channel regulation remains unclear. Here, using the pituitary GH3 cell line as a model, we investigated whether CaV3 channel expression is under the control of GCs, and if their actions are mediated by transcriptional and/or post-transcriptional mechanisms. RT-PCR and western blot analyses showed that CaV3.1 but not CaV3.2 and CaV3.3 channels is expressed in the GH3 cells, and patch clamp recordings confirmed that Ca2+ currents through low voltage-activated channels were decreased after chronic treatment with GCs. Consistent with this, total plasma membrane expression of CaV3.1 protein as analyzed by cell-surface biotinylation assays and semi-quantitative western blotting was also down-regulated, while quantitative real-time RT-PCR analysis revealed a significant decrease of CaV3.1 mRNA expression in the treated cells. In contrast, patch-clamp recordings on HEK-293 cells stably expressing recombinant CaV3.1 channels showed that Ca2+ currents were not affected by GC treatment. These results suggest that decreased transcription is a likely mechanism to explain the inhibitory actions of GCs on the functional expression of native CaV3.1 channels.

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Acknowledgments

This work was supported by funds from Conacyt to RF. We thank Drs. M. E. Mendoza (Cinvestav-IPN, Mexico) and J. C. Gomora (IFC-UNAM, Mexico) for the generous gift of the cell lines and Dr. M. Hernandez (Cinvestav-IPN, Mexico) and D. Mornet (INSERM ERI 25 Muscle et Pathologies, France) for the anti-actin and anti-β-dystroglycan antibodies, respectively. We are also indebted to J. Arikkath for critically reviewing the manuscript.

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Author notes

  1. Oscar Hernández-Hernández

    Present address: Inserm U781, Clinique Maurice Lamy, Hopital Necker-EM, 149 rue de Sèvres, 75015, Paris, France

Authors and Affiliations

  1. Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies of the National Polytechnic Institute, Cinvestav-IPN, Mexico City, Mexico

    Traudy Avila

  2. Department of Cell Biology, Cinvestav-IPN, Avenida IPN 2508, Colonia Zacatenco, 07300, Mexico City, Mexico

    Oscar Hernández-Hernández, Angélica Almanza, Mercedes Urban & Ricardo Felix

  3. Institute of Physiology, University of Puebla, Puebla, Mexico

    Angélica Almanza & Enrique Soto

  4. Division of Genetics, Northeast Biomedical Research Center, Mexican Institute of Social Security (IMSS), Monterrey, Mexico

    Mario Bermúdez de León

  5. Department of Genetics and Molecular Biology, Cinvestav-IPN, Mexico City, Mexico

    Bulmaro Cisneros

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Correspondence to Ricardo Felix.

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Traudy Avila and Oscar Hernández-Hernández contributed equally to this work.

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Avila, T., Hernández-Hernández, O., Almanza, A. et al. Regulation of CaV3.1 Channels by Glucocorticoids. Cell Mol Neurobiol 29, 1265–1273 (2009). https://doi.org/10.1007/s10571-009-9422-2

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