Effect of lead on the erythrocyte (Ca2+,Mg2+)-ATPase activity Calmodulin involvement

Summary I have investigated the effect of lead on the erythrocyte ghosts (Ca²⁺,Mg²⁺)-ATPase, with special attention to the role of calmodulin in this phenomena. Under regular incubation conditions, lead inhibits the enzyme with an IC₅₀ of 6.0 µM. The presence of exogenously added calmodulin apparently does not change this inhibitory value. DTT added during the incubation period does not affect the inhibitory action of lead. However, when the membranes are preincubated with DTT, an important IC₅₀ displacement is observed, either with or without added calmodulin. Since [¹²⁵I]calmodulin binding to the membranes is enhanced when lead is used, the possibility of a lead/calmodulin complex that optimally stimulates the enzyme using lead concentrations between 1.0 and 10.0 µM, is suggested. Based on the experimental data, I propose two well defined actions of lead; first, an inhibitory action upon the ATPase above 1.0 µM lead, most probably related to essential sullphydryl groups in the enzyme; and second, a direct action of lead upon calmodulin at lead concentrations below 1.0 µM.A preliminary report has been presented at the 5^th European Bioenergetics Conference. Aberystwyth, Wales. 20–26 July 1988. EBEC Reports. vol 5; p294 (1988).