Estradiol inhibits depolarization-evoked exocytosis in PC12 cells via N-type voltage-gated calcium channels

Kelly L. Adams, Marc M. Maxson, Lisa Mellander, Remco H.S. Westerink, Andrew G. Ewing

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1235-1242
Number of pages8
JournalCellular and Molecular Neurobiology
Volume30
Issue number8
DOIs
StatePublished - Nov 2010

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Cell Biology

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