Estradiol affect Na-dependent Ca2+ efflux from synaptosomal mitochondria

Abstract

The effects of gonadal steroid hormone, 17 beta-estradiol (E-2), in vitro on rat brain mitochondria Ca2+ movement were investigated. Intrasynaptosomal mitochondria Ca2+ uptake via an energy-driven Ca2+ uniporter have K-m = 112.73 +/- 7.3 mu mol.l(-1) and V-max = 21.97 +/- 1.7 nmol Ca-45(2+) mg(-1). Ca2+ release trough a Na+/Ca2+ 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 Ca-45(2+) 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.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 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.