Methylmercury-induced inhibition of regulatory volume decrease in astrocytes: characterization of osmoregulator efflux and its reversal by amiloride.
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.
Aschner
M
M
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, USA. maschner@bgsm.edu
Vitarella
D
D
Allen
J W
JW
Conklin
D R
DR
Cowan
K S
KS
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*
D008767:Methylmercury Compounds; D009498:Neurotoxins; D017923:Sodium-Hydrogen Exchangers; D013654:Taurine; D007294:Inositol; D000584:Amiloride; D011188:Potassium