Inactivation of depolarization-induced calcium uptake in rat brain synaptosomes

The inactivation of depolarization-induced Ca uptake into rat brain synaptosomes was demonstrated biochemically by comparing 45Ca fluxes after various intervals of predepolarization achieved by abruptly increasing [K+]o. The chemical composition of the medium was maintained throughout the predepolarization and Ca uptake steps. Under these conditions, inactivation was dependent on depolarization, i.e., basal unstimulated Ca uptake in the presence of 5 mM [K+]o did not inactivate. Inactivation of stimulated Ca uptake was dependent on the predepolarization interval, moderately dependent on [Ca]o and relatively independent of membrane potential, i.e., [K+]o and ions such as Ni2+ and Co2+ that blocked Ca uptake. Both cinnarizine and lidoflazine blocked stimulated Ca uptake in a concentration-dependent manner without affecting the % inactivation. Although the amount of stimulated uptake increased greatly between 10 and 30 degrees C, the % inactivation was unaffected by temperature. These findings suggest that inactivation of the presynaptic Ca uptake is an intrinsic property of the channel independent of calcium uptake.