Interactions of methylmercury with rat primary astrocyte cultures: inhibition of rubidium and glutamate uptake and induction of swelling.
The ability of astrocytes to sequester MeHg may indicate an astrocyte-mediated role in MeHg's neurotoxicity. Hence, studies were undertaken to assess the effects of MeHg on metabolic functions in cultured astrocytes. MeHg (10(-5) M) significantly inhibited the initial rate (5 min) of uptake of 86RbCl, used as a tracer for K+. 86RbCl uptake was also sensitive to the omission of medium Na+. MeHg (10(-5) M) also markedly inhibited the initial rate of uptake (1 min) of the Na(+)-dependent uptake of [3H]L-glutamate. A second neurotoxin, MnCl2 (0-5 x 10(-4) M), did not alter [3H]glutamate or 86RbCl uptake. MeHg, but not MnCl2, also stimulated the release of intracellular 86Rb+ in a dose-dependent fashion. This effect could be prevented by the administration of MeHg as the glutathione conjugate. These observations support the hypothesis that the astrocyte plasma membrane is an important target for MeHg's toxic effect and specifically that small concentrations of this organometal inhibit the ability of astrocytes to maintain a transmembrane K+ gradient. This would be expected to compromise the ability of astrocytes to control extracellular K+ either by spatial buffering or active uptake, resulting in cellular swelling. We therefore studied volume changes in astrocytes using uptake of [14C]3-O-methyl-D-glucose, in attached cells in response to exposure to MeHg. Exposure to MeHg (0-5 x 10(-4) M) caused a marked increase in the cell volume that was proportional to concentrations of MeHg.
Aschner
M
M
Department of Pharmacology and Toxicology, Albany Medical College, NY 12208.
Eberle
N B
NB
Miller
K
K
Kimelberg
H K
HK
D019325:3-O-Methylglucose; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D002712:Chlorides; D005971:Glutamates / Q000378:metabolism*; D017895:Manganese Compounds; D020149:Manganese Poisoning; D008757:Methylglucosides / Q000494:pharmacology; D008767:Methylmercury Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012413:Rubidium / Q000378:metabolism*; D012414:Rubidium Radioisotopes
D002712:Chlorides; D005971:Glutamates; D017895:Manganese Compounds; D008757:Methylglucosides; D008767:Methylmercury Compounds; D012414:Rubidium Radioisotopes; D019325:3-O-Methylglucose; D012413:Rubidium; C025340:manganese chloride