Estradiol reduces calcium currents in rat neostriatal neurons via a membrane receptor

Paul G. Mermelstein*, Jill B. Backer, D. James Surmeier

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

568 Scopus citations


Until recently, steroid hormones were believed to act only on cells containing intracellular receptors. However, recent evidence suggests that steroids have specific and rapid effects at the cellular membrane. Using whole-cell patch-clamp techniques, 17β-estradiol was found to reduce Ba2+ entry reversibly via Ca2+ channels in acutely dissociated and cultured neostriatal neurons. The effects were sex-specific, i.e., the reduction of Ba2+ currents was greater in neurons taken from female rats. 17β- Estradiol primarily targeted L-type currents, and their inhibition was detected reliably within seconds of administration. The maximum reduction by 17β-estradiol occurred at picomolar concentrations. 17β-Estradiol conjugated to bovine serum albumin also reduced Ba2+ currents, suggesting that the effect occurs at the membrane surface. Dialysis with GTPγS prevented reversal of the modulation, suggesting that 17β-estradiol acts via G-protein activation. 17α-Estradiol also reduced Ba2+ currents but was significantly less effective than 17β-estradiol. Estriol and 4- hydroxyestradiol were found to reduce Ba2+ currents with similar efficacy to 17β-estradiol, whereas estrone and 2-methoxyestriol were less effective. Tamoxifen also reduced Ba2+ currents but did not occlude the effect of 17β-estradiol. These results suggest that at physiological concentrations, 17β-estradiol can have immediate actions on neostriatal neurons via nongenomic signaling pathways.

Original languageEnglish (US)
Pages (from-to)595-604
Number of pages10
JournalJournal of Neuroscience
Issue number2
StatePublished - Jan 15 1996


  • Ca current
  • estradiol
  • estrogen receptor
  • neostriatum
  • neuromodulation
  • nongenomic
  • patch clamp
  • steroid

ASJC Scopus subject areas

  • General Neuroscience


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