Specificity and reversibility of the inhibition by HgCl2 of glutamate transport in astrocyte cultures.
Inhibition of glutamate transport is a potential indirect cause of excitotoxic damage by glutamate in the CNS. The mercuric ion, the form in which metallic mercury vapor is believed to exert its neurotoxic action, is a known inhibitor of amino acid transport. This study examines the specificity with which HgCl2 inhibits glutamate transport in mouse cerebral astrocytes by means of comparative measurements of 2-deoxyglucose uptake. Uptake of 2-deoxyglucose is an index of glucose utilization that reflects the function of Na+,K+-ATPase and hexokinase, and is sensitive to Na+ entry. The kinetic parameters, ionic dependence, and substrate specificity of glutamate transport in these astrocyte cultures were consistent with the commonly occurring system designated X-AG. Acute exposure to 0.5 microM HgCl2 inhibited by 50% the initial rate of glutamate transport but did not affect 2-deoxyglucose uptake. Glutamate transport was not detectably inhibited by Al2+, Pb2+, Co2+, Sr2+, Cd2+, or Zn2+ (10 microM as chlorides). The inhibitory action of 0.5 microM HgCl2 on glutamate transport was rapidly reversible. The action of 1-2 microM HgCl2 was progressive when exposures were extended to 1-3 h, and was more slowly reversible. These results suggest that Hg2+ can impair glial glutamate transport reversibly at exposure levels that do not compromise some other vital cell functions.
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002413:Cations, Divalent; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D007700:Kinetics; D008627:Mercuric Chloride / Q000494:pharmacology*; D051379:Mice; D012964:Sodium / Q000494:pharmacology
D002413:Cations, Divalent; D005971:Glutamates; D018698:Glutamic Acid; D008627:Mercuric Chloride; D003847:Deoxyglucose; D012964:Sodium