Estradiol affect Na-dependent Ca2+ efflux from synaptosomal mitochondria.
The effects of gonadal steroid hormone, 17beta-estradiol (E2), in vitro on rat brain mitochondria Ca2+ movement were investigated. Intrasynaptosomal mitochondria Ca2+ uptake via an energy-driven Ca2+ uniporter have Km = 112.73 +/- 7.3 micromol x l(-1) and Vmax = 21.97 +/- 1.7 nmol 45Ca2+ mg(-1). Ca2+ release trough a Na+/Ca2+ antiporter was measured with a Km for Na+ of 43.7 +/- 2.6 mmol x l(-1), and Vmax of 1.5 +/- 0.3 nmol 45Ca2+ mg(-1). Addition of estradiol in preincubation mixture did not affect the uptake of Ca2+ mediated by the ruthenium red-sensitive uniporter, while it produced biphasic effect on Na-dependent Ca2+ efflux. Estradiol at concentrations up to 1 nmol x l(-1) decreased the efflux significantly (63% inhibition with respect to the control), and at concentrations above 10 nmol x l(-1) increased it exponentially. The maximum inhibiting concentration of estradiol (0.5 nmol x l(-1)) increased the affinity of the uniporter (Km reduced by about 30%), without affecting significantly the capacity (Vmax) for Na+. The results presented suggest that estradiol inhibits Na-dependent Ca2+ efflux from mitochondria and acts on mitochondrial retention of Ca2+, which may modulate mitochondrial and consequently synaptosomal content of Ca2+, and in this way exerts its role in the homeostasis of calcium in nerve terminals.
Horvat
A
A
Laboratory of Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, Belgrade, Yugoslavia. ahorvat@rt270.vin.bg.ac.yu
Petrović
S
S
Nedeljković
N
N
Martinović
J V
JV
Nikezić
G
G
D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D008928:Mitochondria / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012430:Ruthenium Red / Q000378:metabolism; D012964:Sodium / Q000378:metabolism* / Q000493:pharmacokinetics; D013574:Synaptosomes / Q000378:metabolism; D013997:Time Factors
D012430:Ruthenium Red; D004958:Estradiol; D012964:Sodium; D006180:Proton-Translocating ATPases; D002118:Calcium