Estrogens directly potentiate neuronal L-type Ca2+ channels. Academic Article uri icon


  • L-type voltage-gated Ca(2+)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 Ca(2+) influx in hippocampal neurons, which is required for neuroprotection and potentiation of LTP. The mechanism by which estrogen rapidly induces this Ca(2+) 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.

published proceedings

  • Proc Natl Acad Sci U S A

altmetric score

  • 1

author list (cited authors)

  • Sarkar, S. N., Huang, R., Logan, S. M., Yi, K. D., Dillon, G. H., & Simpkins, J. W

citation count

  • 81

complete list of authors

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

publication date

  • September 2008