Estradiol affect Na-dependent Ca ²⁺ efflux from synaptosomal mitochondria

Abstract

The effects of gonadal steroid hormone, 17β-estradiol (E 2 ), in vitro on rat brain mitochondria Ca 2+ movement were investigated. Intrasynaptosomal mitochondria Ca 2+ uptake via an energy-driven Ca 2+ uniporter have K m = 112.73 ± 7.3 μmol.l -1 and V max = 21.97 ± 1.7 nmol 45 Ca 2+ mg -1 . Ca 2+ release trough a Na + /Ca 2+ antiporter was measured with a K m for Na + of 43.7 ± 2.6 mmol.l -1 , and V max of 1.5 ± 0.3 nmol 45 Ca 2+ mg -1 . Addition of estradiol in preincubation mixture did not affect the uptake of Ca 2+ mediated by the ruthenium red-sensitive uniporter, while it produced biphasic effect on Na-dependent Ca 2+ efflux. Estradiol at concentrations up to 1 nmol.l -1 decreased the efflux significantly (63% inhibition with respect to the control), and at concentrations above 10 nmol.l -1 increased it exponentially. The maximum inhibiting concentration of estradiol (0.5 nmol.l -1 ) increased the affinity of the uniporter (K m reduced by about 30%), without affecting significantly the capacity (V max ) for Na + . The results presented suggest that estradiol inhibits Na-dependent Ca 2+ efflux from mitochondria and acts on mitochondrial retention of Ca 2+ , which may modulate mitochondrial and consequently synaptosomal content of Ca 2+ , and in this way exerts its role in the homeostasis of calcium in nerve terminals.