Estrogens directly potentiate neuronal L-type Ca2+ channels

Saumyendra N. Sarkar, Ren-Qi Huang, Shaun M. Logan, Don Yi Kun, Glenn H. Dillon, James W. Simpkins

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Abstract

L-type voltage-gated Ca2+channels (VGCC) play an important role in dendritic development, neuronal survival, and synaptic plasticity. Recent studies have demonstrated that the gonadal steroid estrogen rapidly induces Ca2+ influx in hippocampal neurons, which is required for neuroprotection and potentiation of LTP. The mechanism by which estrogen rapidly induces this Ca2+ influx is not clearly understood. We show by electrophysiological studies that extremely low concentrations of estrogens acutely potentiate VGCC in hippocampal neurons, hippocampal slices, and HEK-293 cells transfected with neuronal L-type VGCC, in a manner that was estrogen receptor (ER)-independent. Equilibrium, competitive, and whole-cell binding assays indicate that estrogen directly interacts with the VGCC. Furthermore, a L-type VGCC antagonist to the dihydropyridine site displaced estrogen binding to neuronal membranes, and the effects of estrogen were markedly attenuated in a mutant, dihydropyridine-insensitive L-type VGCC, demonstrating a direct interaction of estrogens with L-type VGCC. Thus, estrogen-induced potentiation of calcium influx via L-type VGCC may link electrical events with rapid intracellular signaling seen with estrogen exposure leading to modulation of synaptic plasticity, neuroprotection, and memory formation.

Original languageEnglish
Pages (from-to)15148-15153
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number39
DOIs
StatePublished - 30 Sep 2008

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Estrogens
Neuronal Plasticity
Neurons
HEK293 Cells
Estrogen Receptors
Steroids
Calcium
Membranes

Keywords

  • Estradiol
  • Estrogen receptors
  • Memory
  • Signaling

Cite this

Sarkar, Saumyendra N. ; Huang, Ren-Qi ; Logan, Shaun M. ; Kun, Don Yi ; Dillon, Glenn H. ; Simpkins, James W. / Estrogens directly potentiate neuronal L-type Ca2+ channels. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 39. pp. 15148-15153.
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Estrogens directly potentiate neuronal L-type Ca2+ channels. / Sarkar, Saumyendra N.; Huang, Ren-Qi; Logan, Shaun M.; Kun, Don Yi; Dillon, Glenn H.; Simpkins, James W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 39, 30.09.2008, p. 15148-15153.

Research output: Contribution to journalArticleResearchpeer-review

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