Cellular and Molecular Neurobiology

, Volume 30, Issue 8, pp 1235–1242 | Cite as

Estradiol Inhibits Depolarization-Evoked Exocytosis in PC12 Cells via N-Type Voltage-Gated Calcium Channels

Original Research


Fast neuromodulatory effects of 17-β-estradiol (E2) on cytosolic calcium concentration ([Ca2+] i ) have been reported in many cell types, but little is known about its direct effects on vesicular neurotransmitter secretion (exocytosis). We examined the effects of E2 on depolarization-evoked [Ca2+] i in PC12 cells using fluorescence measurements. Imaging of [Ca2+] i with FURA-2 revealed that depolarization-evoked calcium entry is inhibited after exposure to 10 nM and 10 μM E2. Calcium entry after exposure to 50 μM E2 decreases slightly, but insignificantly. To relate E2-induced changes in [Ca2+] i to functional effects, we measured exocytosis using amperometry. It was observed that E2 in some cells elicits exocytosis upon exposure. In addition, E2 inhibits depolarization-evoked exocytosis with a complex concentration dependence, with inhibition at both physiological and pharmacological concentrations. This rapid inhibition amounts to 45% at a near physiological level (10 nM E2), and 50% at a possible pharmacological concentration of 50 μM. A small percentage (22%) of cells show exocytosis during E2 exposure (“Estrogen stimulated”), thus vesicle depletion could possibly account (at least partly) for the E2-induced inhibition of depolarization-evoked exocytosis. In cells that do not exhibit E2-stimulated release (“Estrogen quiet”), the E2-induced inhibition of exocytosis is abolished by a treatment that eliminates the contribution of N-type voltage-gated calcium channels (VGCCs) to exocytosis. Overall, the data suggest that E2 can act on N-type VGCCs to affect secretion of neurotransmitters. This provides an additional mechanism for the modulation of neuronal communication and plasticity by steroids.


Catecholamine secretion Calcium channels Calcium homeostasis Amperometry 17-β-Estradiol Exocytosis 





Beta form of the estrogen receptor


Membrane estrogen receptor


Pheochromocytoma cells


Voltage-gated calcium channel



This study was supported by funding from the National Institutes of Health and the Swedish Science Research Council (Vetenskapsrådet or VR). A.G.E. is supported by a Marie Curie Chair from the European Union 6th Framework.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Kelly L. Adams
    • 1
    • 3
  • Marc M. Maxson
    • 2
  • Lisa Mellander
    • 3
  • Remco H. S. Westerink
    • 4
  • Andrew G. Ewing
    • 1
    • 2
    • 3
  1. 1.Department of ChemistryThe Pennsylvania State UniversityUniversity ParkUSA
  2. 2.The Huck Institutes of the Life Sciences, Neuroscience InstituteThe Pennsylvania State UniversityUniversity ParkUSA
  3. 3.Department of ChemistryUniversity of GothenburgGöteborgSweden
  4. 4.Neurotoxicology Research Group, Institute for Risk Assessment SciencesUtrecht UniversityUtrechtThe Netherlands

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