Date of Award

Summer 1996

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program/Concentration

Biomedical Sciences

Committee Director

Dieter K. Bartschat

Committee Member

Peter F. Blackmore

Committee Member

barbara Y. Hargrave

Committee Member

Gerald J. Pepe

Committee Member

Paul H. Ratz

Abstract

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.

Comments

A dIssertation Submitted to the Faculty of Old Dominion University and Eastern Virginia Medical School in Partial Fulfillment of the Requirement for the Degree of Doctor of Philosophy in Biomedical Sciences.

DOI

10.25777/sj0e-0275

ISBN

9780591048674

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