title: Methylmercury-induced inhibition of regulatory volume decrease in astrocytes: characterization of osmoregulator efflux and its reversal by amiloride.
abstract: Swelling of neonatal rat primary astrocyte cultures by hypotonic media leads to regulatory volume decrease (RVD) and the resumption of resting cell volume. RVD is associated with activation of conductive K+ and Cl- channels, allowing for the escape of KCl, as well as the release of osmoregulators, such as taurine and myoinositol. As we have previously shown [D. Vitarella, H.K. Kimelberg, M. Aschner, Inhibition of RVD in swollen rat primary astrocyte cultures by methylmercury (MeHg) is due to increase amiloride-sensitive Na+ uptake, Brain Res. 732 (1996) 169-178.], MeHg, when added to hypotonic buffer inhibits RVD, primarily due to increased cellular permeability to Na+ via the Na+/H+ antiporter. The present study was, therefore, undertaken to assess the ability of cation-anion cotransport blockers to reverse the inhibitory effect of MeHg on RVD in swollen astrocytes, and to further characterize MeHg-induced changes in astrocytic osmoregulatory release processes. The studies demonstrate the following: (1) MeHg-induced inhibition of RVD is partially inhibited by the Na+/H+ antiporter blocker, amiloride, but not SITS (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid), DIDS (4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid), furosemide or bumetanide; (2) exposure of swollen astrocytes to MeHg is associated with specific effects on osmoregulatory release, leading to significant inhibition of taurine release and a significant increase in potassium and myoinositol release compared with release in hypotonic conditions.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, USA. maschner@bgsm.edu
authors.forename: M
authors.initials: M
authors.lastname: Aschner
authors.forename: D
authors.initials: D
authors.lastname: Vitarella
authors.forename: J W
authors.initials: JW
authors.lastname: Allen
authors.forename: D R
authors.initials: DR
authors.lastname: Conklin
authors.forename: K S
authors.initials: KS
authors.lastname: Cowan
mesh_terms: D000584:Amiloride / Q000627:therapeutic use*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000473:pathology; D048429:Cell Size / Q000187:drug effects*; D002478:Cells, Cultured; D007294:Inositol / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D008767:Methylmercury Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity*; D009498:Neurotoxins / Q000633:toxicity*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D013654:Taurine / Q000378:metabolism; D018675:Toxicity Tests; D014882:Water-Electrolyte Balance / Q000187:drug effects*
chemical_list: D008767:Methylmercury Compounds; D009498:Neurotoxins; D017923:Sodium-Hydrogen Exchangers; D013654:Taurine; D007294:Inositol; D000584:Amiloride; D011188:Potassium