17β-estradiol modulates mitochondrial Ca2+ flux in rat caudate nucleus and brain stem

S. Petrović, M. Milošević, D. Drakulić, I. Grković, M. Stanojlović, N. Mitrović, A. Horvat

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Abstract

The aim of this study was to examine the rapid non-genomic effect of 17β-estradiol (E2) on Ca2+ transport in mitochondria isolated from the nerve terminals (synaptosomes) of caudate nuclei (NC) and brain stems (BS) of ovariectomised female rats. In physiological conditions no effect of E2 on Ca2+ influx into synaptosomal mitochondria through ruthenium red (RR)-sensitive uniporter was observed. However, in the presence of uncoupling agent carbonyl cyanide4-(trifluoromethoxy)phenylhydrazone (FCCP) (1μmol/l), pre-treatment with 0.5nmol/l E2 protected mitochondrial membrane potential and consequently increased Ca2+ influx (2.3-fold in NC and 3.1-fold in BS). At the same time, 0.5nmol/l E2 by increasing the affinity of mitochondrial Na+/Ca2+ exchanger for Na+ inhibited mitochondrial Ca2+ efflux in NC and BS by about 40%. Also, the specific binding of physiological E2 concentrations (0.1-10nmol/l) to isolated synaptosomal mitochondria was detected. Using membrane impermeable E2 bound to bovine serum albumin and selective inhibitor of mitochondrial Na+/Ca2+ exchanger, we obtained that E2's action on mitochondrial Ca2+ efflux at least partially is due to the direct effects on the mitochondrial membrane and/or Na+/Ca2+ exchanger located in inner mitochondrial membrane. Our results implicate E2 as a modulator of Ca2+ concentration in mitochondrial matrix, and ultimately in the cytosol. Given the vital role of Ca2+ in regulation of total nerve cells activity, especially energy metabolism, neurotransmission and directing the cells toward survival or cell death, the effects on mitochondrial Ca2+ transport could be one of the important modes of E2 neuromodulatory action independent of the genome.

Original languageEnglish (US)
Pages (from-to)32-40
Number of pages9
JournalNeuroscience
Volume220
DOIs
StatePublished - Sep 18 2012

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Keywords

  • Brain stem
  • Ca transport
  • Caudate nucleus
  • Estradiol
  • Rat brain
  • Synaptosomal mitochondria

Cite this

Petrović, S., Milošević, M., Drakulić, D., Grković, I., Stanojlović, M., Mitrović, N., & Horvat, A. (2012). 17β-estradiol modulates mitochondrial Ca2+ flux in rat caudate nucleus and brain stem. Neuroscience, 220, 32-40. https://doi.org/10.1016/j.neuroscience.2012.06.040