Age-dependent neurotoxicity in rats chronically exposed to low levels of lead: Calcium homeostasis in central neurons

Chronic exposure of rats to low level (1 mg/kg. day) lead ingestion starting at a prenatal age reduced the number of IP₃ receptors in ER and reduced the capacity of IP₃ to increase Ca(i)²⁺ in permeabilized neurons obtained from the cerebral cortices. Chronic exposure of adult rats to a comparable dose of lead did not cause these changes. A second stimulation of samples with IP₃ in the absence of extracellular Ca²⁺ did not further increase Ca(i)²⁺ suggesting the depletion of the IP₃ sensitive Ca²⁺ pool. However, when IP₄ preceded the second IP₃ stimulation, an increase in Ca(i)²⁺ was noted. In samples exposed to La³⁺ followed by IP₃, Ca(i)²⁺ remained elevated and did not return to the base line which suggests that the IP₃ sensitive pool of Ca²⁺ is removed from neurons primarily by active extrusion. When IP₄ was added to the samples exposed to La³⁺ and IP₃, a significant decrease in Ca(i)²⁺ was noted. These observations suggest that IP₄ refills Ca²⁺ stores possibly by redistributing Ca²⁺ from cytoplasm to the stores. Chronic low level lead ingestion starting prenatally or at an adult age did not impair the effect of IP₄ on Ca(i)²⁺ suggesting that the IP₄ induced redistribution of Ca²⁺ from cytoplasm to intracellular Ca²⁺ stores is not effected by chronic exposure of rats to low level lead ingestion. The present observations that chronic exposure of rats to low level lead ingestion does not effect the capacity of GTP to increase Ca(i)²⁺ but attenuated the combined effects of GTP and IP₃ in neurons further suggest that IP₃ receptors are specifically down-regulated by prenatal lead exposure.