title: Inhibition of mitochondrial Na+-dependent Ca²+ efflux by 17β-estradiol in the rat hippocampus.
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.
authors: Laboratory for Molecular Biology and Endocrinology, Institute of Nuclear Sciences "Vinča", University of Belgrade, PO Box 522, 11001 Belgrade, Serbia.
authors: S
authors: S
authors: Petrović
authors: N
authors: N
authors: Veličković
authors: I
authors: I
authors: Stanojević
authors: M
authors: M
authors: Milošević
authors: D
authors: D
authors: Drakulić
authors: M
authors: M
authors: Stanojlović
authors: A
authors: A
authors: Horvat
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism
chemical_list: D004967:Estrogens; D004958:Estradiol; D012964:Sodium; D002118:Calcium