Inhibition of mitochondrial Na +-dependent Ca 2+ efflux by 17β-estradiol in the rat hippocampus

S. Petrović, N. Veličković, I. Stanojević, M. Milošević, D. Drakulić, Milos Stanojlovic, A. Horvat

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Abstract

Our results, as well as those of others, have indicated that 17β-estradiol (E2) exerts its nongenomic effects in neuronal cells by affecting plasma membrane Ca 2+ flux. In neuronal cells mitochondria possess Ca 2+ buffering properties as they both sequester and release Ca 2+. The goal of this study was to examine the rapid non-genomic effect of E2 on mitochondrial Ca 2+ transport in hippocampal synaptosomes from ovariectomised rats. In addition, we aimed to determine if, and to what extent, E2 receptors participated in mitochondrial Ca 2+ transport modulation by E2 in vitro. E2-specific binding and Ca 2+ transport was monitored. At physiological E2 concentrations (0.1-1.5 nmol/L), specific E2 binding to mitochondria isolated from hippocampal synaptosomes was detected with a B max. and K m of 37.6±2.6 fmol/mg protein and 0.69±0.14 nmol/L of free E2, respectively. The main mitochondrial Ca 2+ influx mechanism is the Ruthenium Red-sensitive uniporter driven by mitochondrial membrane potential. Despite no effect of E2 on Ca 2+ influx, a physiological E2 concentration (0.5 nmol/L) protected mitochondrial membrane potential and consequently Ca 2+ influx from the uncoupling agent carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (1 μmol/L). In neuronal cells the predominant mitochondrial Ca 2+ efflux mechanism is the Na +/Ca 2+ exchanger. E2 caused Ca 2+ efflux inhibition (by 46%) coupled with increased affinity of the Na +/Ca 2+ exchanger for Na +. Using E2 receptor (ERα and ERβ) antagonists and agonists, we confirmed ERβ's involvement in E2-induced mitochondrial membrane potential protection as well as Ca 2+ efflux inhibition. In summary, our results indicate that the non-genomic neuromodulatory role of E2 in rat hippocampus is achieved by affecting mitochondrial Ca 2+ transport via, in part, mitochondrial ERβ.

Original languageEnglish (US)
Pages (from-to)195-204
Number of pages10
JournalNeuroscience
Volume192
DOIs
StatePublished - Sep 29 2011

Keywords

  • Ca transport
  • Estradiol
  • Estradiol receptors
  • Mitochondria
  • Rat hippocampus

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    Petrović, S., Veličković, N., Stanojević, I., Milošević, M., Drakulić, D., Stanojlovic, M., & Horvat, A. (2011). Inhibition of mitochondrial Na +-dependent Ca 2+ efflux by 17β-estradiol in the rat hippocampus. Neuroscience, 192, 195-204. https://doi.org/10.1016/j.neuroscience.2011.06.030