ALTERATIONS IN CALCIUM HOMEOSTASIS ON LEAD-EXPOSURE IN RAT SYNAPTOSOMES

The effects of lead on Ca2+ homeostasis in nerve terminals was studied . Incubation with lead in vitro stimulated the activity of calmodulin and the maximum effect was observed at 30 muM lead, higher concentrati ons had an inhibitory effect. In vivo exposure to lead increased the a ctivity of calmodulin by 45 %. Lead had an inhibitory effect on Ca2+AT Pase activity in both calmodulin-rich and calmodulin-depleted synaptic plasma membranes, the IC50 values for inhibition being 13.34 and 16.6 9 muM respectively. Exogenous addition of calmodulin (5 mug) and gluta thione (1 mM) to calmodulin rich synaptic plasma membranes reversed th e inhibition by IC50 Concentration of lead. In vivo exposure of lead a lso significantly reduced the Ca2+ATPase activity, resulting in an inc rease in intrasynaptosomal calcium. Concomitant with the increase in i ntrasynaptosomal calcium, lipid peroxidation values also increased sig nificantly in lead-treated animals. In addition lead also had an inhib itory effect on depolarization induced Ca2+ uptake and the inhibition was found to be a competitive one. The results suggest that lead exert s its toxic effects by modifications of the intracellular calcium mess enger system which would have serious consequences on neuronal functio ning.