INHIBITION OF REGULATORY VOLUME DECREASE IN SWOLLEN RAT PRIMARY ASTROCYTE CULTURES BY METHYLMERCURY IS DUE TO INCREASED AMILORIDE-SENSITIVENA+ UPTAKE

Primary astrocyte cultures from neonatal rats were swollen by exposure to hypotonic buffer with and without 10 mu M methylmercury (MeHg). We investigated the effects of MeHg on K+ (using Rb-86), taurine, D-aspa rtate (a non metabolizable analogue of glutamate) and Na+ fluxes durin g regulatory volume decrease (RVD), with an electrical impedance metho d for determination of cell volume, coupled with on-line measurements of efflux of radioactive ions and amino acids. Addition of 10 mu M MeH g completely inhibited RVD in swollen astrocytes, increased the uptake of Na-22(+), increased Rb-86 release, and decreased H-3-taurine relea se. There was no effect on the rare of release of H-3-D-aspartate from swollen astrocytes. 0.5 mM amiloride completely inhibited MeHg-induce d increased Na+ influx during RVD, while 1 mM furosemide had no effect . When Na+ in the hypotonic buffer was replaced with N-methyl-D-glucam ine (NMDG), RVD in the presence of MeHg was indistinguishable from con trols. These results indicate that MeHg increases cellular permeabilit y to ions such as Na+ and K+, and that an increase in Na+ permeability via Na+/H+ exchange, offsetting K+ loss, is the primary mechanism in its inhibition of RVD in swollen astrocytes.