Methylmercury-induced astrocytic swelling is associated with activation of the Na+/H+ antiporter, and is fully reversed by amiloride.
Astrocytes are a known 'sink' for brain methylmercury (MeHg) deposition. Yet, the significance of the preferential accumulation of MeHg within these cells is imprecisely defined. To determine whether MeHg in isotonic buffer has the potential to interfere with homeostatic functions, we measured its effect on astrocytic volume using an electrical impedance method [E.R. O'Connor, H.K. Kimelberg, C.R. Keese, I. Giaever, Electrical impedance method for measuring volume changes in astrocytes, Am. J. Physiol. 264 (1993) C471-C478.]. In addition, we have characterized the alterations in astrocytic ion permeability associated with exposure to this organometal. The results show that MeHg rapidly induces astrocytic swelling, and that this effect is secondary to increased astrocytic Na+ uptake. Furthermore, the effect of MeHg on astrocytic swelling is completely inhibited by amiloride, but not by SITS (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid), furosemide, or bumetanide. Accordingly, increased cellular permeability to Na+ via the Na+/H+ antiporter is invoked as the primary mechanism of MeHg-induced astrocytic swelling.
Aschner
M
M
Departments of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA. maschner@bgsm.edu
Vitarella
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Allen
J W
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Conklin
D R
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Cowan
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KS
D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects*; D001692:Biological Transport / Q000187:drug effects; D002034:Bumetanide / Q000494:pharmacology; D002478:Cells, Cultured; D005665:Furosemide / Q000494:pharmacology; D008767:Methylmercury Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012413:Rubidium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology*
D008767:Methylmercury Compounds; D017923:Sodium-Hydrogen Exchangers; D002034:Bumetanide; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D001224:Aspartic Acid; D000584:Amiloride; D005665:Furosemide; D012413:Rubidium