Lead Activation of a Developmentally Regulated Calcium Channel in Rat Hippocampal Nerve Terminals

<p>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.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Year dc:date.available

1996

Author dc:creator

• Rhodes, Troy E.

Contributors dc:contributor

• Dieter K. Bartschat
• Peter F. Blackmore
• barbara Y. Hargrave
• Gerald J. Pepe
• Paul H. Ratz

• Lead activation
• Calcium channel
• Rats
• Nerve
• Neurology
• Toxicology

Identifier

9780591048674

OAI identifier oai:identifier

oai:digitalcommons.odu.edu:biomedicalsciences_etds-1074