Low level lead (Pb2+) exposure may produce lasting deficits in learning and memory by altering calcium (Ca2+) dependent processes. Isolated presynaptic nerve terminals from rat hippocampus were loaded with the intracellular (Ca2+) indicator Fura-2. The changes in cytoplasmic free calcium ([Ca2+]i) were measured by stopped-flow fluorescence spectroscopy following depolarization with elevated potassium on a millisecond time scale (Lentzner et al., 1992). Depolarization promoted a rapid increase in Ca2+i which occured in two kinetically distinguishable phases: a fast component, representing the activity of rapidly inactivating Ca2+ channels (τ ~ 60 msec), and a slow component, which is comprised of slowly inactivating Ca2+ channels (τ ~ 1sec) and Na+/Ca2+ exchange operating in the reverse mode. Low concentrations of Pb2+ (0.1-0.5 μΜ ) blocked competitively both the rapidly and slowly inactivating channels. At higher concentrations (≥1μΜ) , Pb2+ permeated the rapidly inactivating channels. Pb2+ permeation was accompanied by a subsequent rise in intracellular Ca2+ even in the absence of extracellular Ca2+. The rise in Ca2+ was reduced by thapsigargin, suggesting Pb2+ activates the release of Ca2+ from intracellular stores, possibly an IP3 sensitive store. The Ca2+ release was greatest in younger animals and gradually declined during postnatal development
