Document Detail


Block of 45Ca uptake into synaptosomes by methylmercury: Ca++- and Na+-dependence.
MedLine Citation:
PMID:  2918475     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Block of Ca++ influx into isolated nerve terminals by the neurotoxicant methylmercury (MeHg) was studied for its dependence on extracellular Ca++ and Na+. Depolarization-independent entry of 45Ca++ was determined in rat forebrain synaptosomes incubated in 5 mM K+ solution. 45Ca++ uptake was similarly measured after 1 ("fast" phase) or 10 sec ("total") of elevated K+ (41.25 mM)-induced depolarization or after 10 sec of elevated K+-induced depolarization after synaptosomes had been predepolarized for 10 sec in Ca++- and MeHg-free solutions ("slow" phase). In 5 mM K+ solutions, MeHg concentrations of 125 microM and greater significantly reduced synaptosomal 45Ca++ uptake measured during 1 or 10 sec of incubation. In K+-depolarized synaptosomes, the estimated IC50 for block of total, fast and slow 45Ca++ uptake by MeHg is 75 microM; 250 microM MeHg reduced uptake by approximately 90%. The reversibility of block by extracellular Ca++ was tested by increasing the extracellular Ca++ concentration from 0.01 to 1.15 mM. When compared to control, 50 microM MeHg reduced total uptake of 45Ca++ by greater than or equal to 70% and reduced fast uptake by 20 to 60% at all concentrations of extracellular Ca++ tested. At Ca++ concentrations of 0.01 to 0.15 mM, MeHg (50 microM) reduced slow uptake by 75 to 90%, but did not affect slow uptake at higher Ca++ concentrations (greater than or equal to 0.30 mM). When the dependence of block of 45Ca++ uptake on extracellular Na+ was tested, equivalent levels of inhibition were caused by MeHg (25 microM) for fast uptake by synaptosomes in Na+-containing and Na+-free solutions.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
T J Shafer; W D Atchison
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  248     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1989 Feb 
Date Detail:
Created Date:  1989-04-03     Completed Date:  1989-04-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  696-702     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium / metabolism*,  physiology
Cell Membrane Permeability / drug effects
Male
Methylmercury Compounds / pharmacology*
Rats
Rats, Inbred Strains
Sodium / pharmacology,  physiology*
Synaptosomes / metabolism*
Grant Support
ID/Acronym/Agency:
1-KO4-ES00178/ES/NIEHS NIH HHS; ES03299/ES/NIEHS NIH HHS; GM07392-11A1/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Methylmercury Compounds; 7440-23-5/Sodium; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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