Glucocorticoids prolong CA2+ transients in hippocampal-derived h19-7 neurons by repressing the plasma membrane CA2+-atpase-1

Aditi Bhargava, Robert S. Mathias, James (Jim) McCormick, Mary F. Dallman, David Pearce

Research output: Contribution to journalArticlepeer-review


Calcium ions (Ca2+) play an important role in mediating an array of structural and functional responses in cells. In hippocampal neurons, elevated glucocorticoid (GC) levels, as seen during stress, perturb calcium homeostasis and result in altered neuronal excitability and viability. Ligand- and volt-age-gated calcium channels have been the presumed targets of hormonal regulation; however, circumstantial evidence has suggested the possibility that calcium extrusion might be an important target of GC regulation. Here we demonstrate that GC-induced repression of the plasma membrane Ca2+-ATPase-1 (PMCA1) is an essential determinant of intracellular Ca2+ levels ([Ca2+]i) in cultured hippocampal H19-7 cells. In particular, GC treatment caused a prolongation of agonist-evoked elevation of [Ca2+]i that was prevented by the expression of exogenous PMCA1. Furthermore, selective inhibition of PMCA1 using the RNA interference technique caused prolongation of Ca2+ transients in the absence of GC treatment. Taken together, these observations suggest that GC-mediated repression of PMCA1 is both necessary and sufficient to increase agonist-evoked Ca2+ transients by down-regulating Ca2+ extrusion mechanisms in the absence of effects on calcium channels. Prolonged exposure to GCs, resulting in concomitant accumulation of [Ca2+]i, is likely to compromise neuronal function and viability.

Original languageEnglish (US)
Pages (from-to)1629-1637
Number of pages9
JournalMolecular Endocrinology
Issue number7
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism


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