METHYLMERCURY-INDUCED INHIBITION OF REGULATORY VOLUME DECREASE IN ASTROCYTES - CHARACTERIZATION OF OSMOREGULATOR EFFLUX AND ITS REVERSAL BYAMILORIDE

Swelling of neonatal rat primary astrocyte cultures by hypotonic media leads to regulatory volume decrease (RVD) and the resumption of resti ng 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 previou sly 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, primaril y due to increased cellular permeability to Na+ via the Na+/H+ antipor ter. The present study was, therefore, undertaken to assess the abilit y of cation-anion cotransport blockers to reverse the inhibitory effec t of MeHg on RVD in swollen astrocytes, and to further characterize Me Hg-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, b ut not SITS 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 significan t inhibition of taurine release and a significant increase in potassiu m and myoinositol release compared with release in hypotonic condition s. (C) 1998 Elsevier Science B.V. All rights reserved.