Mechanism of destabilization of Ca2+ homeostasis in brain nerve cells caused by toxic glutamate treatment

In mammalian central neurons overstimulation of glutamate (Glu) receptors i nduces destabilization of neuronal Ca2+ homeostasis which is caused mainly by an impairment of Ca2+ extrusion systems of the neuronal membrane and inh ibition of mitochondrial electrophoretic Ca2+ uptake. The latter effect is due to a profound mitochondrial depolarization, which, according to the exi sting data, is due to opening of the permeability transition pore (PTP) in response to mitochondrial Ca2+ overload and overproduction of free oxygen r adicals and NO. Mechanism of deterioration of Ca2+ extrusion following a to xic Glu challenge is not fully clarified. It is known only that during a pr olonged Glu treatment some factors are accumulated in the neuron, which can suppress both Na+/Ca2+ exchange and Ca2+/H+ pump. Among them, a decrease i n ATP level, cytoplasmic increase in Na+ concentration, lowering of pH(i), overproduction of reactive oxygen species and some products of lipid peroxi dation should be mentioned. Contribution of each of these factors to the fi nal effect of the Glu-induced destabilization of [Ca2+](i) homeostasis is u nder investigation.